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The Pancreas and Lipoprotein Metabolism

Henry N. Ginsberg, Ira J. Goldberg

10.1002/cphy.cp070222

Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Lipoproteins
1.1 Lipoprotein Structure and Composition
1.2 Plasma Lipid Enzymes
2 Transport of Exogenous (Dietary) Lipids
3 Transport of Endogenous Lipids
3.1 Regulation of the Assembly and Secretion of Apoprotein B‐100‐Containing Lipoproteins
3.2 Very‐Low‐Density Lipoprotein Catabolism
3.3 Very‐Low‐Density Lipoprotein Metabolism in Diabetes Mellitus
3.4 Low‐Density Lipoprotein Production and Catabolism
3.5 Low‐Density Lipoprotein Metabolism in Diabetes Mellitus
3.6 Metabolism of Apoprotein A‐I‐Containing Lipoproteins
3.7 Apoprotein A‐I‐Containing Lipoproteins in Diabetes Mellitus
Figure 1. Figure 1.

Transport of chylomicrons and chylomicron remnants. A: In normal individuals, intestinal chylomicrons undergo lipolysis of triglyceride in adipose tissue and muscle after interacting with lipoprotein lipase. The resulting chylomicron remnant is taken up by the liver, mainly via the low‐density lipoprotein (LDL) receptor. B: In poorly controlled type 1 and type 2 patients, lipoprotein lipase is decreased and chylomicron triglyceride levels are increased. There also appears to be a block in the uptake of chylomicron remnants by the liver, possibly related to decreased LDL receptor activity.
Figure 2. Figure 2.

Transport of very‐low‐density lipoprotein (VLDL), intermediate‐density lipoprotein (IDL), and low‐density lipoprotein (LDL). A: In normal individuals, VLDL is assembled and secreted from the liver and undergoes lipoprotein lipase mediated hydrolysis of triglyceride in adipose tissue and muscle. This step generates IDL (also called the VLDL remnant), which can either be taken up by the liver, mainly via LDL receptors, or undergo further modification and conversion to LDL. Low‐density lipoprotein delivers cholesterol to tissues throughout the body, although about one‐half of LDL returns to the liver. B: In poorly controlled type 1 diabetes, there is increased hormone sensitive lipase mediated triglyceride lipolysis in adipose tissue. This results in increased free fatty acid flux to the liver, stimulating the assembly and secretion of VLDL. Insulin deficiency also results in diminished lipoprotein lipase activity and reduced lipolysis of VLDL triglyceride. Intermediate‐density lipoprotein and LDL uptake by the liver and other tissues may be reduced because of decreased LDL receptor activity. Thus LDL cholesterol levels can be increased modestly. All of these abnormalities are reversible with tight glycemic control. C: In type 2 diabetes, insulin resistance results in increased release of fatty acids from adipose tissue, increased VLDL assembly and secretion from the liver, and hypertriglyceridemia. Lipoprotein lipase may be normal or decreased, and this will determine the severity of hypertriglyceridemia. Intermediate‐density lipoprotein uptake may be normal or reduced. Low‐density lipoprotein levels are usually normal although LDL is small, dense and cholesterol‐depleted.
Figure 3. Figure 3.

Transport of high‐density lipoprotein (HDL). A: In normal individuals, cholesterol‐depleted HDL is formed by several pathways. This form of HDL, called HDL3 or prebeta HDL can accumulate free cholesterol from cell membranes and extracellular matrix (including blood vessel walls). After esterification of the free cholesterol by lecithin: cholesterol acyltransferase (LCAT), the cholesterol ester rich HDL, now called HDL2, can deliver cholesterol esters to the liver, probably via a receptor called scavenger receptor B1 (SRB1). HDL2 can, however, also transfer its cholesterol ester to very‐low‐density lipoprotein (VLDL) (and chylomicrons, intermediate‐density lipoprotein (IDL) and chylomicron remnants) in an exchange reaction for triglyceride. This exchange is mediated by cholesteryl ester transfer protein (CETP). B and C: In poorly controlled type 1 (B) and in type 2 (C) diabetes, the exchange of HDL cholesterol esters for VLDL triglycerides is stimulated by hypertriglyceridemia. The modified HDL has a lower affinity for apoA‐I which can then dissociate and be removed by the kidneys. Thus, hypertriglyceridemia is associated with low HDL cholesterol and low apoA‐I levels. This may also mean that reverse cholesterol transport and delivery of cholesterol to the liver for excretion as bile will be interrupted.


Figure 1.

Transport of chylomicrons and chylomicron remnants. A: In normal individuals, intestinal chylomicrons undergo lipolysis of triglyceride in adipose tissue and muscle after interacting with lipoprotein lipase. The resulting chylomicron remnant is taken up by the liver, mainly via the low‐density lipoprotein (LDL) receptor. B: In poorly controlled type 1 and type 2 patients, lipoprotein lipase is decreased and chylomicron triglyceride levels are increased. There also appears to be a block in the uptake of chylomicron remnants by the liver, possibly related to decreased LDL receptor activity.



Figure 2.

Transport of very‐low‐density lipoprotein (VLDL), intermediate‐density lipoprotein (IDL), and low‐density lipoprotein (LDL). A: In normal individuals, VLDL is assembled and secreted from the liver and undergoes lipoprotein lipase mediated hydrolysis of triglyceride in adipose tissue and muscle. This step generates IDL (also called the VLDL remnant), which can either be taken up by the liver, mainly via LDL receptors, or undergo further modification and conversion to LDL. Low‐density lipoprotein delivers cholesterol to tissues throughout the body, although about one‐half of LDL returns to the liver. B: In poorly controlled type 1 diabetes, there is increased hormone sensitive lipase mediated triglyceride lipolysis in adipose tissue. This results in increased free fatty acid flux to the liver, stimulating the assembly and secretion of VLDL. Insulin deficiency also results in diminished lipoprotein lipase activity and reduced lipolysis of VLDL triglyceride. Intermediate‐density lipoprotein and LDL uptake by the liver and other tissues may be reduced because of decreased LDL receptor activity. Thus LDL cholesterol levels can be increased modestly. All of these abnormalities are reversible with tight glycemic control. C: In type 2 diabetes, insulin resistance results in increased release of fatty acids from adipose tissue, increased VLDL assembly and secretion from the liver, and hypertriglyceridemia. Lipoprotein lipase may be normal or decreased, and this will determine the severity of hypertriglyceridemia. Intermediate‐density lipoprotein uptake may be normal or reduced. Low‐density lipoprotein levels are usually normal although LDL is small, dense and cholesterol‐depleted.



Figure 3.

Transport of high‐density lipoprotein (HDL). A: In normal individuals, cholesterol‐depleted HDL is formed by several pathways. This form of HDL, called HDL3 or prebeta HDL can accumulate free cholesterol from cell membranes and extracellular matrix (including blood vessel walls). After esterification of the free cholesterol by lecithin: cholesterol acyltransferase (LCAT), the cholesterol ester rich HDL, now called HDL2, can deliver cholesterol esters to the liver, probably via a receptor called scavenger receptor B1 (SRB1). HDL2 can, however, also transfer its cholesterol ester to very‐low‐density lipoprotein (VLDL) (and chylomicrons, intermediate‐density lipoprotein (IDL) and chylomicron remnants) in an exchange reaction for triglyceride. This exchange is mediated by cholesteryl ester transfer protein (CETP). B and C: In poorly controlled type 1 (B) and in type 2 (C) diabetes, the exchange of HDL cholesterol esters for VLDL triglycerides is stimulated by hypertriglyceridemia. The modified HDL has a lower affinity for apoA‐I which can then dissociate and be removed by the kidneys. Thus, hypertriglyceridemia is associated with low HDL cholesterol and low apoA‐I levels. This may also mean that reverse cholesterol transport and delivery of cholesterol to the liver for excretion as bile will be interrupted.

References
 1. Aalto‐Setala, K., E. A. Fisher, X. Chen, T. Chajek‐Shaul, T. Hayek, R. Zechner, A. Walsh, R. Ramakrishnan, H. Ginsberg, and J. L. Breslow. Mechanism of hypertriglyceridemia in human apolipoprotein (Apo) CIII transgenic mice. J. Clin. Invest. 90: 1889–1900, 1992.
 2. Abrams, J. J., H. Ginsberg, and S. M. Grundy. Metabolism of cholesterol and triglycerides in nonketotic diabetes mellitus. Diabetes 31: 903–910, 1982.
 3. Acton, S., A. Rigotti, K. T. Landschulz, S. Xu, H. H. Hobbs, and M. Krieger. Identification of scavenger receptor SR‐BI as a high density lipoprotein receptor. Science 271: 460–461, 1996.
 4. Acton, S., P. E. Scherer, H. F. Lodish, and M. Krieger. Expression cloning of SR‐BI, a CD36‐related class B scavenger receptor. J. Biol. Chem. 33: 21003–21009, 1994.
 5. Adeli, K., and A. Theriault. Insulin modulation of human apolipoprotein B mRNA translation; studies in an in vitro cell‐free system from HepG2 cells. Biochem. Cell Biol. 70: 1301–1312, 1992.
 6. Agardh, C., P. Nilsson‐Ehle, and B. Scherstein. Improvement of the plasma lipoprotein pattern after institution of insulin treatment in diabetes mellitus. Diabetes Care 5: 322–325, 1982.
 7. Alaupovic, P., J. M. Bard, M. Tabella, and D. Shafer. Identification of apoB‐containing lipoprotein families in NIDDM. Diabetes 41: 18–25, 1992.
 8. Arad, Y., R. Ramakrishnan, and H. N. Ginsberg. Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB‐containing lipoproteins: implications for the pathophysiology of apoB production. J. Lipid Res. 31: 567–582, 1990.
 9. Arbeeny, C. M., D. S. Meyers, K. E. Bergquist, and R. E. Gregg. Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. J. Lipid Res. 33: 843–851, 1992.
 10. Assman, G., and H. Schulte. The prospective cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am. Heart J. 116: 1713–1724, 1988.
 11. Austin, M. A., J. L. Breslow, C. H. Hennekens, J. E. Buring, and R. M. Krauss. Low density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260: 1917–1921, 1988.
 12. Austin, M. A., J. D. Brunzell, W. L. Fitch, and R. M. Krauss. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis 10: 520–530, 1990.
 13. Austin, M. A., and J. E. Hokanson. Epidemiology of triglycerides, small dense low‐density lipoprotein, and lipoprotein (a) as risk factors for coronary heart disease. Med. Clin. North Am 78: 99–115, 1994.
 14. Austin, M. A., M. D. King, K. M. Vranizan, and R. M. Krauss. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 82: 495–506, 1990.
 15. Austin, M. A., L. Mykkanen, J. Kuusisto, K. L. Edwards, C. Nelson, S. M. Haffner, K. Pyorala, and M. Laakso. Prospective study of small LDLs as a risk factor for non‐insulin dependent diabetes mellitus in elderly men and women. Circulation 92: 1770–1778, 1995.
 16. Austin, M. A., and J. V. Selby. LDL subclass phenotypes and the risk factors of the insulin resistance syndrome. Int. J. Obes. Relat. Metab. Disord. 19: S22–S26, 1995.
 17. Babirak, S. P., P. H. Iverius, W. Y. Fujimoto, and J. D. Brunzell. Detection and characterization of the heterozygote state for lipoprotein lipase deficiency. Arteriosclerosis 9: 326–334, 1989.
 18. Bagdade, J. D., W. E. Buchanan, T. Kuusi, and M. Taskinen. Persistent abnormalities in lipoprotein composition in noninsulin‐dependent diabetes after intensive insulin therapy. Arteriosclerosis 10: 232–239, 1990.
 19. Bagdade, J. D., J. T. Lane, P. V. Subbaiah, M. E. Otto, and M. C. Ritter. Accelerated cholesteryl ester transfer in noninsulin‐dependent diabetes mellitus. Atherosclerosis 104: 69–77, 1993.
 20. Bagdade, J. D., D. Porte, and E. L. Bierman. Diabetic lipemia: a form of acquired fat‐induced lipemia. N. Engl. J. Med. 276: 427–433, 1967.
 21. Bagdade, J. D., and P. V. Subbaiah. Whole‐plasma and high‐density lipoprotein subfraction surface lipid composition in IDDM men. Diabetes 38: 1226–1230, 1989.
 22. Balasubramaniam, S., S. Venkatesan, K. A. Mitropoulos, and T. J. Peters. The submicrosomal localization of acyl‐coenzyme A:cholesterol acyltransferase and its substrate, and of cholesteryl esters in rat liver. Biochem. J. 174: 863–872, 1978.
 23. Bamberger, M. J., and M. D. Lane. Assembly of very low density lipoprotein in the hepatocyte. Differential transport of apoproteins through the secretory pathway. J. Biol. Chem. 263: 11868–11878, 1988.
 24. Barkia, A., P. Puchois, N. Ghalim, G. Torpier, R. Barbaras, G. Ailhaud, and J. Fruchart. Differential role of apolipoprotein AI‐containing particles in cholesterol efflux from adipose cells. Atherosclerosis 87: 135–146, 1991.
 25. Barrett, P. H., N. Baker, and P. J. Nestel. Model development to describe the heterogeneous kinetics of apolipoprotein B and triglyceride in hypertriglyceridemic subjects. J. Lipid Res. 32: 743–762, 1991.
 26. Barrett‐Connor, E., and T. J. Orchard. Diabetes and heart disease. In: Diabetes in America. Washington, D.C.: U.S. Government Printing Office, NIH Publication 85–1468, Chapter XVI, p. 1–41, 1985.
 27. Barter, P. J., and K. A. Rye. High‐density lipoproteins and coronary heart disease. J. Cardiovasc. Risk 1: 217–221, 1994.
 28. Bartlett, S. M., and G. F. Gibbons. Short‐ and longer‐term regulation of very‐low‐density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. A biphasic effect of insulin. Biochem. J. 249: 37–43, 1988.
 29. Basso, L. V., and R. J. Havel. Hepatic metabolism of free fatty acids in normal and diabetic dogs. J. Clin. Invest. 49: 537–547, 1970.
 30. Baynes, C., A. D. Henderson, W. Richmond, D. G. Johnston, and R. S. Elkeles. The response of hepatic lipase and serum lipoproteins to acute hyperinsulinemia in type 2 diabetes. Eur. J. Clin. Invest. 22: 341–346, 1992.
 31. Beisiegel, U., W. Weber, and G. Bengtsson‐Olivecrona. Lipoprotein lipase enchances the binding of chylomicrons to low density lipoprotein receptor‐related protein. Proc. Natl. Acad. Sci. U.S.A. 88: 8342–8346, 1991.
 32. Beisigel, U., W. Weber, G. Ihrke, J. Herz, and K. K. Stanley. The LDL‐receptor‐related protein, LRP, is an apolipoprotein E‐binding protein. Nature 341: 162–164, 1989.
 33. Ben, Z. O., M. H. Doolittle, R. C. Davis, J. Elovson, and M. C. Schotz. Maturation of lipoprotein lipase. Expression of full catalytic activity requires glucose trimming but not translocation to the cis‐Golgi compartment. J. Biol. Chem. 267: 6219–6227, 1992.
 34. Bensadoun, A., and D. E. Berryman. Genetics and molecular biology of hepatic lipase. Curr. Opin. Lipidol. 7: 77–81, 1996.
 35. Bergman, M., L. I. Gindez, and H. A. Eder. High‐density lipoprotein subclasses in diabetes. Am. J. Med. 81: 488–492, 1986.
 36. Bergman, M., L. I. Gidez, and H. A. Eder. The effect of glipizide on HDL and HDL subclasses. Diabetes Res. 3: 245–248, 1986.
 37. Biesbroeck, B., J. J. Albers, P. W. Wahl, C. R. Weinberg, M. L. Bassett, and E. L. Bierman. Abnormal composition of high‐density lipoproteins in non‐insulin‐dependent diabetics. Diabetes 31: 126–131, 1982.
 38. Bjornsson, O. G., J. M. Duerden, S. M. Bartlett, J. D. Sparks, C. E. Sparks, and G. F. Gibbons. The role of pancreatic hormones in the regulation of lipid storage, oxidation and secretion in primary cultures of rat hepatocytes. Short‐ and long‐term effects. Biochem. J. 281: 381–386, 1992.
 39. Bjornsson, O. G., J. D. Sparks, C. E. Sparks, and G. F. Gibbons. Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP‐dependent protein kinases. Eur. J. Clin. Invest. 24: 137–48, 1994.
 40. Blum, C. B., R. Levy, S. Eisenberg, M. Hall, R. H. Goebel, and M. Berman. High density lipoprotein metabolism in man. J. Clin. Invest. 60: 795–807, 1977.
 41. Borchardt, R. A., and R. A. Davis. Intrahepatic assembly of very low density lipoproteins. Rate of transport out of the endoplasmic reticulum determines rate of secretion. J. Biol. Chem. 262: 16394–16402, 1987.
 42. Borén, J., M. Wettesten, A. Sjöberg, T. Thorlin, G. Bondjers, O. Wiklund, and S.‐O. Olofsson. The assembly and secretion of ApoB 100 containing lipoproteins in HepG2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly. J. Biol. Chem. 265: 10556–10564, 1990.
 43. Bostrom, K., J. Boren, M. Wettesten, A. Sjoberg, G. Bondjers, O. Wiklund, P. Carlsson, and S. Olofsson. Studies on the assembly of Apo B‐100‐containing lipoproteins in HepG2 cells. J. Biol. Chem. 263: 4434–4442, 1988.
 44. Bostrom, K., M. Wettesten, J. Boren, G. Bondjers, O. Wiklund, and S. Olofsson. Pulse‐chase studies of the synthesis and intracellular transport of apolipoprotein B‐100 in HepG2 cells. J. Biol. Chem. 261: 13800–13806, 1986.
 45. Bradley, W. A., S. L. Hwang, J. B. Karlin, A. H. Lin, S. C. Prasad, J. Gotto, and S. H. Gianturco. Low‐density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very‐low‐density lipoprotein to low‐density lipoproteins. J. Biol. Chem. 259: 14728–14735, 1984.
 46. Breckenridge, W. C., J. A. Little, G. Steiner, A. Chow, and M. Poapst. Hypertriglyceridemia associated with deficiency of apolipoprotein C‐II. N. Engl. J. Med. 298: 1265–1273, 1978.
 47. Breckenridge, W. C., J. A. Little, and P. Alaupovic. Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis 45: 161–179, 1982.
 48. Brindley, D. N., and A. M. Salter. Hormonal regulation of the hepatic low density lipoprotein receptor and the catabolism of low density lipoproteins: relationship with the secretion of very low density lipoproteins. Prog. Lipid Res. 30: 349–360, 1991.
 49. Brinton, E. A., S. Eisenberg, and J. L. Breslow. A low‐fat diet decreases high density lipoprotein (HDL) cholesterol levels by decreasing HDL apolipoprotein transport rates. J. Clin. Invest. 85: 144–151, 1990.
 50. Brinton, E. A., S. Eiseberg, and J. L. Breslow. Human HDL cholesterol levels are determined by apoA‐I fractional catabolic rate, which correlates inversely with estimate of HDL particle size. Arterioscler. Thromb. 14: 707–720, 1994.
 51. Brinton, E. A., S. Eisenberg, and J. L. Breslow. Increased apo A‐I and apo A‐II fractional catabolic rate in patients with low high density lipoprotein‐cholesterol levels with or without hypertriglyceridemia. J Clin. Invest. 87: 536–544, 1991.
 52. Brinton, E. A., J. F. Oram, and E. L. Bierman. The effect of variations in lipid composition of high‐density lipoprotein on its interaction with receptors on human fibroblasts. Biochim. Biophys. Acta 920: 68–75, 1987.
 53. Brown, M. S., and J. L. Goldstein. How LDL receptors influence cholesterol and atherosclerosis. Sci. Am. 251: 58–66, 1984.
 54. Brown, W. V., and M. L. Baginsky. Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein. Biochem. Biophys. Res. Commun. 46: 375–381, 1972.
 55. Bruce, C., and A. R. Tall. Cholesteryl ester transfer proteins, reverse cholesterol transport, and atherosclerosis. Curr. Opin. Lipidol. 6: 306–311, 1995.
 56. Brunzell, J. D., D. J. Porte, and E. L. Bierman. Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes). Metabolism 24: 1123–1137, 1975.
 57. Calvo, C., N. Ulloa, R. Del Pozo, and C. Verdugo. Decreased activation of lecithin: cholesterol acyltransferase by glycated apolipoprotein A‐I. Eur. J. Clin. Chem. Clin. Biochem. 31: 217–220, 1993.
 58. Calvo, C., and C. Verdugo. Association in vivo of glycated apolipoprotein A1 with high density lipoproteins. Eur. J. Clin. Chem. Clin. Biochem. 30: 3–5, 1992.
 59. Carlson, L. A., and D. Ballantyne. Changing relative proportions of apolipoproteins CII and CIII of very low density lipoproteins in hypertriglyceridaemia. Atherosclerosis 23: 563–568, 1976.
 60. Carr, T. P., R. L. Hamilton, Jr., and L. L. Rudel. ACAT inhibitors decrease secretion of cholesteryl esters and apolipoprotein B by perfused livers of African green monkeys. J. Lipid Res. 36: 25–36, 1995.
 61. Castro Cabezas, M., T. W. de Bruin, H. W. de Valk, C. C. Shoulders, H. Jansen, and D. Willem Erkelens. Impaired fatty acid metabolism in familial combined hyperlipidemia. A mechanism associating hepatic apolipoprotein B overproduction and insulin resistance. J. Clin. Invest. 92: 160–168. 1993.
 62. Chait, A., J. J. Albers, and J. D. Brunzell. Very low density lipoprotein overproduction in genetic forms of hypertriglyceridemia. Eur. J. Clin. Invest. 10: 17–22, 1980.
 63. Chait, A., E. L. Bierman, and J. J. Albers. Low density lipoprotein receptor activity in cultured human skin fibroblasts: mechanism of insulin‐induced stimulation. J. Clin. Invest. 64: 1309–1319, 1979.
 64. Chait, A., R. L. Brazg, D. L. Tribble, and R. M. Krauss. Susceptibility of small, dense, low‐density, lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am. J. Med. 94: 350–356, 1993.
 65. Chait, A., D. M. Foster, J. J. Albers, R. A. Failor, and J. D. Brunzell. Low density lipoprotein metabolism in familial combined hyperlipidemia and familial hypercholesterolemia: kinetic analysis using an integrated model. Metabolism 35: 697–704, 1986.
 66. Chait, A., H. T. Robertson, and J. D. Brunzell. Chylomicronemia syndrome in diabetes mellitus. Diabetes Care 4: 343–353, 1979.
 67. Chappell, D. A., G. L. Fry, M. A. Waknitz, L. E. Muhonen, M. W. Pladett, P. H. Iverius, and D. K. Strickland. Lipoprotein lipase induces catabolism of normal triglyceride‐rich lipoproteins via the low density lipoprotein receptor in vitro. J. Biol. Chem. 268: 14168–14175, 1992.
 68. Chen, M., J. L. Breslow, W. Li, and T. Leff. Transcriptional regulation of the apoC‐III gene by insulin in diabetic mice: correlation with changes in plasma triglyceride levels. J. Lipid Res. 35: 1918–1924, 1994.
 69. Cheung, M. C., and L. Albertazzi. Characterization of lipoprotein particles isolated by immunoaffinity chromatography. J. Biol. Chem. 259: 12201–12209, 1984.
 70. Chisolm, G. M., K. C. Irwin, M. S. Penn. Lipoprotein oxidation and lipoprotein‐induced cell injury in diabetes. Diabetes 41 (Suppl. 1): 61–66, 1992.
 71. Choi, S. Y., and A. D. Cooper. A comparison of the roles of the low density lipoprotein (LDL) receptor and the LDL receptor‐related protein/α‐macroglobulin receptor in chylomicron remnant removal in the mouse in vivo. J. Biol. Chem. 268: 15804–15811, 1993.
 72. Chuck, S. L., and V. R. Lingappa. Pause transfer: a topogenic sequence in apolipoprotein B mediates stopping and restarting of translocation. Cell 68: 9–21, 1992.
 73. Chuck, S. L., Z. Yao, B. D. Blackhart, B. J. McCarthy, and V. R. Lingappa. New variation on the translocation of proteins during early biogenesis of apolipoprotein B. Nature 346: 382–385, 1990.
 74. Cianflone, K. M., Z. Yasruel, M. A. Rodriguez, D. Vas, and A. D. Sniderman. Regulation of apoB secretion from HepG2 cells: evidence for a critical role for cholesteryl ester synthesis in the response to a fatty acid challenge. J. Lipid Res. 31: 2045–2055, 1990.
 75. Cladaras, C., M. Hadzopoulou‐Cladaras, R. T. Nolte, D. Atkinson, and V. I. Zannis. The complete sequence and structural analysis of human apolipoprotein B‐100: relationship between apoB‐100 and apoB‐48 forms. EMBO J. 5: 3495–3507, 1986.
 76. Clark, A. B., and S. H. Quarfordt. Apolipoprotein effects on the lipolysis of perfused triglyceride by heparin‐immobilized milk lipase. J. Biol. Chem. 260: 4778–1783, 1985.
 77. Cohn, J. S., D. A. Wagner, S. D. Cohn, J. S. Millar, and E. J. Schaefer. Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B‐100 and high density lipoprotein Apo A‐I production in human subjects using deuterated leucine. Effect of fasting and feeding. J. Clin. Invest. 85: 804–811, 1990.
 78. Corsi, A. K., and R. Schekman. Mechanism of polypeptide translocation into the endoplasmic reticulum. J. Biol. Chem. 271: 30299–30302, 1996.
 79. Craig, W. Y., R. Nutik, and A. D. Cooper. Regulation of apoprotein synthesis and secretion in the human hepatoma HepG2. The effect of exogenous lipoprotein. J. Biol. Chem. 263: 13880–13890, 1988.
 80. Cruickshanks, K. J., T. J. Orchard, and D. J. Becker. The cardiovascular risk profile of adolescents with insulin‐dependent diabetes mellitus. Diabetes Care 8: 118–124, 1985.
 81. Curtiss, L. K., and J. L. Witztum. Plasma apolipoproteins A‐I, A‐II, B, C‐I and E are glycosylated in hyperglycaemic diabetic subjects. Diabetes 34: 452–61, 1985.
 82. D'Antonio, J. A., D. Ellis, B. H. Doft, D. J. Becker, A. L. Drash, L. H. Kuller, and T. J. Orchard. Diabetes complications and glycemie control. The Pittsburgh Prospective Insulin‐Dependent Diabetes Cohort Study: status report after 5 years of IDDM. Diabetes Care 12: 694–700, 1989.
 83. Dammerman, M., L. A. Sandkuijl, J. L. Halaas, W. Chung, and J. L. Breslow. An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3′ untranslated region polymorphisms. Proc. Natl. Acad. Sci. U.S.A. 90: 4562–4566, 1993.
 84. Dashti, N.. The effect of low density lipoproteins, cholesterol, and 25‐hydroxycholesterol on apolipoprotein B gene expression in HepG2 cells. J. Biol. Chem. 267: 7160–7169, 1992.
 85. Dashti, N., D. L. Williams, and P. Alaupovic. Effects of oleate and insulin on the production rates and cellular mRNA concentrations of apolipoproteins in HepG2 cells. J. Lipid Res. 30: 1365–1373, 1989.
 86. Davignon, J., R. E. Gregg, and C. F. Sing. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8: 1–21, 1988.
 87. Davis, R. A., A. B. Prewett, D. C. F. Chan, J. J. Thompson, R. A. Borchardt, and W. R. Gallaher. Intrahepatic assembly of very low density lipoproteins: immunologic characterization of apolipoprotein B in lipoproteins and hepatic membrane fractions and its intracellular distribution. J. Lipid Res. 30: 1185–1196, 1989.
 88. Davis, R. A., R. N. Thrift, C. C. Wu, and K. E. Howell. Apolipo protein B is both integrated into and translocated across the endoplasmic reticulum membrane. Evidence for two functionally distinct pools. J. Biol. Chem. 265: 10005–10011, 1990.
 89. de Silva, H. V., S. J. Lauer, J. Wang, W. S. Simonet, K. H. Weisgraber, R. W. Mahley, and J. M. Taylor. Overexpression of human apolipoprotein C‐III in transgenic mice results in an accumulation of apolipoprotein B48 remnants that is corrected by excess apolipoprotein E. J. Biol. Chem. 269: 2324–2335, 1994.
 90. Deckelbaum, R. J., S. Eisenberg, M. Fainaru, Y. Barenholz, and T. Olivecrona. In vitro production of human plasma low density lipoprotein‐like particles. J. Biol. Chem. 254: 6079–6087, 1979.
 91. Deckelbaum, R. J., E. Granot, Y. Oschry, L. Rose, and S. Eisenberg. Plasma triglyceride determines structure‐composition in low and high density lipoproteins. Arteriosclerosis 4: 225–231, 1984.
 92. Defronzo, R. A., and A. M. Goodman. Efficacy of metformin in patients with non‐insulin‐dependent diabetes mellitus. N. Engl. J. Med. 333: 588–589, 1995.
 93. de Graaf, J., J. C. Hendriks, P. N. Demacker, and A. F. Stalenhoef. Identification of multiple dense LDL subfractions with enhanced susceptibility to in vitro oxidation among hypertriglyceridemic subjects. Normalization after clofibrate treatment. Arterioscler. Thromb. 13: 712–719, 1993.
 94. Demant, T., L. A. Carlson, L. Holmquist, F. Karpe, P. Nilsson‐Ehle, C. J. Packard, and J. Sheperd. Lipoprotein metabolism in hepatic lipase deficiency: studies on the turnover of apolipoprotein B and on the effect of hepatic lipase on high density lipoprotein. J. Lipid Res. 29: 1603–1611, 1988.
 95. Descamps, O., D. Bilheimer, and J. Herz. Insulin stimulates receptor‐mediated uptake of ApoE‐enriched lipoproteins and activated alpha2–macroglobulin in adipocytes. J. Biol. Chem. 268: 974–981, 1993.
 96. Devery, R., and G. H. Tomkin. The effect of insulin and catecholamines on the activities of 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase and acyl‐coenzyme A: cholesterol‐O‐acyltransferase in isolated rat hepatocytes. Diabetologia 29: 122–124, 1997.
 97. De Wikinski, R. L., W. L. Henao, and C. R. Figueroa. Detection of intermediate density lipoproteins in the plasma of diabetic patients. Medicina 42: 265–272, 1982.
 98. Dixon, J. L., R. Chattapadhyay, T. Huima, C. M. Redman, and D. Banerjee. Biosynthesis of lipoprotein: location of nascent ApoAI and ApoB in the rough endoplasmic reticulum of chicken hepatocytes. J. Cell Biol. 117: 1161–1169, 1992.
 99. Dixon, J. L., S. Furukawa, and H. N. Ginsberg. Oleate stimulates secretion of apolipoprotein B‐containing lipoproteins from HepG2 cells by inhibiting early intracellular degradation of apolipoprotein B. J. Biol. Chem. 266: 5080–5086, 1991.
 100. Dixon, J. L., and H. N. Ginsberg. Regulation of hepatic secretion of apolipoprotein B‐containing lipoproteins: information obtained from cultured liver cells. J. Lipid Res. 34: 167–179, 1993.
 101. Dixon, J. L., T. Huima, and D. Banerjee. 1989. Location of nascent apoproteins A‐I and B in the rough endoplasmic reticulum. J. Cell Biol. 109: 148a, 1989.
 102. Doolittle, M. H., O. Ben‐Zeev, J. Elovson, D. Martin, and T. G. Kirchgessner. The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. J. Biol. Chem. 265: 4570–4577, 1990.
 103. Duerden, J. M., and G. F. Gibbon. Restoration in vitro of normal rates of very‐low‐density lipoprotein triacylglycerol and apoprotein B secretion in hepatocyte cultures from diabetic rats. Biochem. J. 294: 167–171, 1993.
 104. Dunn, F. L., P. A. Cleary, H. G. Schrott, M. J. Oexman, B. Castle, M. W. Steffes, M. Lopes‐Virella, and D. M. Nathan. Lipid and lipoprotein levels in patients with insulin‐dependent diabetes mellitus: results from the Diabetes Control and Complications Trial. In: 8th Int. Symp. Atherosclerosis, Rome, Amsterdam: Experta Medica, 1988, p. 9–13.
 105. Dunn, F. L., A. Pietri, and P. Raskin. Plasma lipid and lipoprotein levels with continuous subcutaneous insulin infusion in type I diabetes mellitus. Ann. Intern. Med. 95: 426–431, 1981.
 106. Dunn, F. L., P. Raskin, D. W. Bilheimer, and S. M. Grundy. The effect of diabetic control on very low‐density lipoprotein‐triglyceride metabolism in patients with type II diabetes mellitus and marked hypertriglyceridemia. Metabolism 33: 117–123, 1984.
 107. Eckel, R. H., J. J. Albers, M. C. Cheung, P. W. Wahl, F. T. Lindgren, and E. L. Bierman. High‐density lipoprotein composition in insulin‐dependent diabetes mellitus. Diabetes 30: 132–138, 1981.
 108. Eckel, R. H., I. J. Goldberg, L. Steiner, T. J. Yost, and J. R. Paterniti, Jr.. Plasma lipolytic activity. Relationship to postheparin lipolytic activity and evidence for metabolic regulation. Diabetes 37: 610–615, 1988.
 109. Eckel, R. H., T. J. Yost, and D. R. Jensen. Alterations in lipoprotein lipase in insulin resistance. Int. J. Obes. Relat. Metab. Disord. 19 (Suppl.): S16–S21, 1995.
 110. Egusa, G., W. F. Beltz, S. M. Grundy, and B. V. Howard. Influence of obesity on the metabolism of apolipoprotein B in humans. J. Clin. Invest. 76: 596–603, 1985.
 111. Eisenberg, S.. High density lipoprotein metabolism. J. Lipid Res. 25: 1017–1058, 1984.
 112. Eisenberg, S., D. Gavish, Y. Oschry, M. Fainaru, and R. J. Deckelbaum. Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment. J. Clin. Invest. 74: 470–482, 1984.
 113. Eisenberg, S., and E. Sehayek. Remnant particles and their metabolism. Baillieres Clin. Endocrinol. Metab. 9: 739–753, 1995.
 114. Eisenberg, S., E. Sehayek, T. Olivecrona, and I. Vlodavsky. Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix. J. Clin. Invest. 90: 2013–2021, 1992.
 115. Elkeles, R. S., and J. Hambley. The effects of fasting and streptozocin diabetes on hepatic triglyceride lipase activity in the rat. Diabetes 26: 58–60, 1977.
 116. Elkeles, R. S., J. Wu, and J. Hambrey. Haemoglobin Al, blood glucose, and high‐density lipoprotein cholesterol in insulin‐requiring diabetics. Lancet 2: 547–548, 1978.
 117. Falko, J. M., T. M. O'Dorisio, and S. Cataland. Improvement of high‐density lipoprotein‐cholesterol levels: ambulatory type I diabetics treated with the subcutaneous insulin pump. JAMA 247: 37–39, 1982.
 118. Fan, J., J. Wang, A. Bensadoun, S. J. Lauer, Q. Dang, R. W. Mahley, and J. M. Taylor. Overexpression of hepatic lipase in transgenic rabbits leads to a marked reduction of plasma high density lipoproteins and intermediate density lipoproteins. Proc. Natl. Acad. Sci. U.S.A. 91: 8724–8772, 1994.
 119. Feingold, K. R., C. Grunfeld, M. Pang, W. Doerrler, and R. M. Krauss. LDL subclass phenotypes and triglyceride metabolism in non‐insulin‐dependent diabetes. Arterioscler. Thromb. 2: 1496–502, 1992.
 120. Fidge, N., P. Nestel, T. Ishikawa, M. Reardon, and T. Billington. Turnover of apoproteins A‐I and A‐II of high density lipoprotein and the relationship to other lipoproteins in normal and hyperli‐pidemic individuals. Metabolism 29: 643–653, 1980.
 121. Foster, D. M., A. Chait, J. J. Albers, R. A. Failor, C. Harris, and J. D. Brunzell. Evidence for kinetic heterogeneity among human low density lipoproteins. Metabolism 35: 685–696, 1986.
 122. Fried, S. K., C. D. Russell, N. L. Grauso, and R. E. Brolin. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J. Clin. Invest. 92: 2191, 1993.
 123. Fuki, I. V., S. N. Preobrazhensky, A. Y. Mishavin, N. G. Bushmakina, G. B. Menshickov, V. S. Repin, and R. S. Karpov. Effect of cell cholesterol content on apolipoprotein B secretion and LDL receptor activity in the human hepatoma cell line, HepG2. Biochim. Biophys. Acta 1001: 235–238, 1989.
 124. Fungwe, T. V., L. Cagen, H. G. Wilcox, and M. Heimberg. Regulation of hepatic secretion of very low density lipoprotein by dietary cholesterol. J. Lipid Res. 33: 179–191, 1992.
 125. Furukawa, S., N. Sakata, H. N. Ginsberg, and J. L. Dixon. Studies of the sites of intracellular degradation of apolipoprotein B in HepG2 cells. J. Biol. Chem. 267: 22630–22638, 1992.
 126. Gabor, J., M. Spain, and N. Kalant. Composition of serum very low density and high density lipoproteins in diabetes. Clin. Chem. 26: 1261–1265, 1980.
 127. Galeano, N. F., R. Milne, Y. L. Marcel, M. T. Walsh, E. Levy, T. Ngu'yen, A. Gleeson, Y. Arad, L. Witte, M. Al‐Haideri, S. C. Rumsey, and R. J. Deckelbaum. Apoprotein B structure and receptor recognition of triglyceride‐rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride‐rich LDL of normal size. J. Biol. Chem. 269: 511–519, 1994.
 128. Garcia, M. J., P. M. McNamara, T. Gordon, and W. B. Kannell. Morbidity and mortality in diabetics in the Framingham population: sixteen year follow‐up study. Diabetes 23: 105–111, 1974.
 129. Gianturco, S. H., J. Gotto, S. C. Hwang, J. B. Karlin, A. H. Y. Lin, S. C. Prasad, and W. A. Bradley. Apolipolipoprotein E mediates uptake of Sf 100–400 hypertriglyceridemic very low density lipoproteins by the low density lipoprotein receptor path‐way in normal human fibroblasts. J. Biol. Chem. 258: 4526–4533, 1983.
 130. Gibbons, G. F.. Hyperlipidaemia of diabetes. Clin. Sci.(Colch.) 71: 477–486, 1986.
 131. Ginsberg, H., I. J. Goldberg, P. Wang‐Iverson, E. Gitler, N. Le, H. S. Gilbert, and W. V. Brown. Increased non‐receptor mediated catabolism of low density lipoprotein apoprotein‐B in subjects with myeloproliferative diseases. Arteriosclerosis 3: 233–241, 1983.
 132. Ginsberg, H., and S. M. Grundy. Effect of caloric restriction on very low density lipoprotein triglyceride metabolism in subjects with diabetes mellitus. Diabetologia 23: 421–25, 1982.
 133. Ginsberg, H., N. Le, J. Melish, D. Steinberg, and W. V. Brown. Effect of a high carbohydrate diet on apoprotein‐B catabolism in man. Metabolism 30: 347–353, 1981.
 134. Ginsberg, H. N.. Very low density lipoprotein metabolism in diabetes mellitus. Diabetes Metab. Rev. 3: 571–589, 1987.
 135. Ginsberg, H. N., A. Jacobs, N. Le, and J. Sandler. Effect of somatostatin induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet. J. Clin. Invest. 70: 1225–1233, 1982.
 136. Ginsberg, H. N., N. Le, and J. C. Gibson. Regulation of the production and catabolism of plasma low density lipoproteins in hypertriglyceridemic subjects. Effect of weight loss. J. Clin. Invest. 75: 614–623, 1985.
 137. Ginsberg, H. N., N. Le, I. J. Goldberg, P. Wang‐Iverson, J. C. Gibson, A. Rubinstein, R. A. Norum, and W. V. Brown. Apolipoprotein B metabolism in subjects with deficiency of apolipoprotein C‐III and A‐I: evidence that apolipoprotein C‐III inhibits lipoprotein lipase in vivo. J. Clin. Invest. 78: 1287–1295, 1986.
 138. Ginsberg, H. N., N. Le, M. P. Short, R. Ramakrishnan, and R. J. Desnick. Suppression of apolipoprotein B production during treatment of cholesteryl ester storage disease with lovastatin: implications for regulation of apolipoprotein B synthesis. J. Clin. Invest. 80: 1692–1697, 1987.
 139. Ginsberg, H. N., C. Ngai, X. Wang, and R. Ramakrishnan. Increased production rates of low density lipoproteins are common in individuals with low plasma levels of high density lipoprotein cholesterol, independent of plasma triglyceride concentrations. Arterioscler. Thromb. 13: 842–851, 1993.
 140. Glasgow, A. M., G. P. August, and W. Hung. Relationship between control and serum lipids in juvenile‐onset diabetes. Diabetes Care 4: 76–80, 1981.
 141. Glaumann, H., A. Bergstrand, and J. L. E. Ericsson. Studies on the synthesis and intracellular transport of lipoprotein particles in rat liver. J. Cell. Biol. 64: 356–377, 1975.
 142. Glosmet, J. A.. The plasma lecithin:cholesterol acyltransferase reaction. J. Lipid Res. 9: 155–167, 1968.
 143. Golay, A., L. Zech, and M. Shi. High density lipoprotein (HDL) metabolism in noninsulin‐dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL. J. Clin. Endocrinol. Metab. 65: 512–518, 1987.
 144. Goldberg, I. J., J. J. Kandel, C. B. Blum, and H. N. Ginsberg. The association of plasma lipoproteins with post‐heparin lipase activities. J. Clin. Invest. 78: 1523–1528, 1986.
 145. Goldberg, I. J., N. Le, H. N. Ginsberg, J. R. Paterniti, and W. V. Brown. The metabolism of apoprotein‐B in the cynomolgus monkey. Am. J. Physiol. 244 (Endocrinol. Metab.: E196–E201, 1983.
 146. Goldberg, L., N. Le, J. Paterniti, H. Ginsberg, and W. V. Brown. Effect of acute inhibition of hepatic triglyceride lipase on very low density lipoprotein metabolism in the cynomolgus monkey. J. Clin. Invest. 70: 1184–1192, 1982.
 147. Gonen, B., N. White, G. Schonfeld, D. Skor, P. Miller, and J. Santiago. Plasma levels of apoprotein B in patients with diabetes mellitus: the effect of glycemic control. Metabolism 34: 675–679, 1985.
 148. Gordon, D. J., J. L. Probstfield, R. J. Garrison, et al. High‐density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 79: 8–15, 1989.
 149. Gordon, T., W. P. Castelli, M. C. Hjortland, W. B. Kannel, and T. R. Dawber. Diabetes blood lipids and the role of obesity in coronary heart disease risk for women. The Framingham study. Ann. Intern. Med. 87: 393–397, 1977.
 150. Gotto, A. M., Jr., H. J. Pownall, and R. J. Havel. Introduction to the plasma lipoproteins. Methods Enzymol. 128: 3–41, 1986.
 151. Green, P. H. R., and R. M. Glickman. Intestinal lipoprotein metabolism. J. Lipid Res. 22: 1153–1173, 1981.
 152. Greenfield, M., O. Kolterman, J. Olefsky, and G. M. Reaven. Mechanism of hypertriglyceridemia in diabetic patients with fasting hyperglycaemia. Diabetologia 18: 441–146, 1980.
 153. Greenfield, M. S., L. Doberne, M. Rosenthal, H. J. Vreman, and G. M. Reaven. Lipid metabolism in non‐insulin‐dependent diabetes mellitus. Arch. Intern. Med. 142: 1498–1500, 1982.
 154. Grosser, J., O. Schrecker, and H. Greten. Function of hepatic triglyceride lipase in lipoprotein metabolism. J. Lipid Res. 22: 437–442, 1981.
 155. Haffner, S. M., D. M. Foster, R. S. Kushwaha, and W. R. Hazzard. Retarded chylomicron apolipoprotein‐B catabolism in type 2 (non‐insulin dependent) diabetic subjects with lipaemia. Diahetologia 26: 349–354, 1984.
 156. Haghpassand, M., D. Wilder, and J. B. Moberly. Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2). J. Lipid Res. 37: 1468–1480, 1996.
 157. Hamo, K., E. A. Nikkila, and T. Kuusi. Plasma HDL‐cholesterol and postheparin plasma hepatic endothelial lipase (HL) activity: relationship to obesity and non‐insulin dependent diabetes (NIDDM). Diabetes 31: 126–131, 1982.
 158. Hashimoto, S., and A. M. Fogelman. Smooth microsomes. A trap for cholesteryl ester formed in hepatic microsomes. J. Biol. Chem. 255: 8678–8684, 1980.
 159. Havel, R. J.. Chylomicron remnants: hepatic receptors and metabolism. Curr. Opin. Lipidol. 6: 312–316, 1995.
 160. Havel, R. J., H. A. Eder, and J. H. Bragdon. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest. 34: 1345–1353, 1955.
 161. Hennessy, L. K., J. Osada, J. M. Ordovas, R. J. Nicolosi, A. F. Stucchi, M. E. Brousseau, and E. J. Schaefer. Effects of dietary fats and cholesterol on liver lipid content and hepatic apolipoprotein A‐I, B, and E and LDL receptor mRNA levels in Cebus monkeys. J. Lipid Res. 33: 351–360, 1992.
 162. Herz, J., U. Hamann, S. Rogne, O. Myklebost, H. Gausepohl, and K. K. Stanley. Surface location and high affinity for calcium of a 500 kd liver membrane protein closely related to the LDL‐receptor suggest a physiological role as lipoprotein receptor. EMBO J. 7: 4119–4127, 1988.
 163. Herz, J., R. C. Kowal, J. L. Goldstein, and M. S. Brown. Proteolytic processing of the 600 kd low density lipoprotein receptor‐related protein (LRP) occurs in a trans‐Golgi compartment. EMBO J. 9: 1769–1776, 1990.
 164. Herz, J., S. Q. Qiu, A. Oesterle, H. V. de Silva, S. Shafi, and R. J. Havel. Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor. Proc. Natl. Acad. Sci. U.S.A. 92: 4611–4615, 1995.
 165. Herz, J., and T. E. Willnow. Lipoprotein and receptor interactions in vivo. Curr. Opin. Lipidol. 6: 97–103, 1995.
 166. Hiramatsu, K., and S. Arimori. Increased superoxide production by mononuclear cells of patients with hypertriglyceridaemia and diabetes. Diabetes 37: 832–837, 1988.
 167. Hiramatsu, K., E. L. Bierman, and A. Chait. Metabolism of low‐density lipoprotein from patients with diabetic hypertriglyceridemia by cultured human skin fibroblasts. Diabetes 34: 8–14, 1985.
 168. Hoeg, J. M., B. L. Vaisman, S. J. Demosky, Jr., S. M. Meyn, G. D. Talley, R. F. Hoyt, Jr., S. Feldman, A. M. Berard, N. Sakai, D. Wood, M. E. Brousseau, S. Marcovina, H. B. Brewer, Jr., and S. Santamarina‐Fojo. Lecithin: cholesterol acyltransferase over‐expression generates hyperalpha‐lipoproteinemia and a nonatherogenic lipoprotein pattern in transgenic rabbits. J. Biol. Chem. 271: 4396–4402, 1996.
 169. Hollenbeck, C. B., Y. Chen, M. S. Greenfield, C. K. Lardinois, and G. M. Reaven. Reduced plasma high density lipoprotein‐cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in noninsulin‐dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 62: 605–608, 1986.
 170. Hoogewerf, A. J., L. A. Cisar, D. C. Evans, and A. Bensadoun. Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. J. Biol. Chem. 266: 16564–16571, 1991.
 171. Horowitz, B. S., I. J. Goldberg, J. Merab, T. Vanni, R. Ramakrishnan, and H. N. Ginsberg. Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A‐I in subjects with low levels of high density lipoprotein cholesterol. J. Clin. Invest. 91: 1743–1752, 1993.
 172. Howard, B. V.. Lipoprotein metabolism in diabetes mellitus. J. Lipid Res. 28: 613–628, 1987.
 173. Howard, B. V., W. F. Abbott, F. Beltz, I. Harper, R. M. Fields, S. M. Grundy, and R. Taskinen. Integrated study of low density lipoprotein metabolism and very low density lipoprotein in non‐insulin‐dependent diabetes. Metabolism 36: 870–877, 1987.
 174. Howard, B. V., J. S. Reitman, B. Vasquez, and L. Zech. Very‐low density lipoprotein triglyceride metabolism in non‐insulin‐dependent diabetes mellitus: relationship to plasma insulin and free fatty acids. Diabetes 32: 271–276, 1983.
 175. Huff, M. W., D. E. Telford, P. H. Barrett, D. W. Bilheimer, and P. J. Gillies. Inhibition of hepatic ACAT decreases ApoB secretion in miniature pigs fed a cholesterol‐free diet. Arterioscler Thromb. 14: 1498–1508, 1994.
 176. Huff, M. W., D. E. Telford, K. Woodcroft, and W. L. P. Strong. Mevinolin and cholestyramine inhibit the direct synthesis of low density lipoprotein apolipoprotein B in miniature pigs. J. Lipid Res. 26: 1175–1186, 1985.
 177. Hughes, T. A., T. S. Clements, P. K. Fairclough, D. S. H. Bell, and J. P. Segrest. Effect of insulin therapy on lipoproteins in non‐insulin dependent diabetes mellitus (NIDDM). Atherosclerosis 67: 105–114, 1987.
 178. Hui, D. Y., T. L. Innerarity, and R. W. Mahley. Lipoprotein binding to canine hepatic membranes. J. Biol. Chem. 256: 5646–5655, 1981.
 179. Ingebritsen, T. S., M. J. H. Geelen, R. A. Parker, K. J. Everson, and J. C. Gibson. Modulation of hydroxymethylglutaryl‐CoA reductase activity, reductase kinase activity, and cholesterol synthesis in rat hepatocytes in response to insulin and glucagon. J. Biol. Chem. 254: 9986–9989, 1979.
 180. Ingram, M. F., and G. S. Shelness. Apolipoprotein B‐100 destined for lipoprotein assembly and intracellular degradation undergoes efficient translocation across the endoplasmic reticulum membrane. J. Lipid Res. 37: 2202–2214, 1996.
 181. Innerarity, T. L., and K. Bostrom. Mutations and variants of apolipoprotein B that affect plasma cholesterol levels. Adv. Exp. Med. Biol. 014: 25–31, 1991.
 182. Ishibashi, S., J. Herz, N. Maeda, J. L. Goldstein, and M. S. Brown. The two‐receptor model of lipoprotein clearance: tests of the hypothesis in “knockout” mice lacking the low density lipoprotein receptor, apolipoproein E, or both proteins. Proc. Natl. Acad. Sci. U.S.A. 91: 4431–435, 1994.
 183. Jackson, T. K., A. I. Salhanick, J. Elovson, M. L. Deichman, and J. M. Amatruda. Insulin regulates apolipoprotein B turnover and phosphorylation in rat hepatocytes. J. Clin. Invest. 86: 1746–1751, 1990.
 184. James, R. W., B. Martin, D. Pometta, J. C. Fruchart, P. Duriez, P. Puchois, J. P. Farriaux, A. Tacquet, T. Demant, R. J. Clegg, A. Munro, M. F. Oliver, C. J. Packard, and J. Shepherd. Apolipoprotein B metabolism in homozygous familial hypercholesterolemia. J. Lipid. Res. 30: 159–169, 1989.
 185. Janus, E. D., A. Nicoll, R. Wootton, P. R. Turner, P. J. Magill, and B. Lewis. Quantitative studies of very low density lipoprotein: conversion to low density lipoprotein in normal controls and primary hyperlipidaemic states and the role of direct secretion of low density lipoprotein in heterozygous familial hypercholesterolaemia. Eur. J. Clin. Invest. 10: 149–159, 1980.
 186. Ji, Z. S., S. J. Lauer, S. Fazio, A. Bensadoun, J. M. Taylor, and R. W. Mahley. Enhanced binding and uptake of remnant lipoproteins by hepatic lipase‐secreting hepatoma cells in culture. J. Biol. Chem. 269: 13429–13436, 1997.
 187. Johnson, W. J., E. P. C. Kilsdonk, A. van Tol, M. C. Phillips, and G. H. Rothblat. Cholesterol efflux from cells to immunopurified subfractions of human high density lipoprotein: LP‐AI and LPOAI/AII. J. Lipid Res. 32: 1993–2000, 1991.
 188. Joven, J., E. Vilella, B. Costa, P. R. Turner, R. Richart, and L. Masana. Concentrations of lipids and apolipoproteins in patients with clinically well‐controlled insulin‐dependent and non‐insulin‐dependent diabetes. Clin. Chem. 35: 813–816, 1989.
 189. Kannell, W. B., and D. L. McGee. Diabetes and cardiovascular risk factors: the Framingham study. Circulation 59: 8–13, 1979.
 190. Kasim, S. E., K. Tseng, K. C. Jen, and S. Khilnani. Significance of hepatic triglyceride lipase activity in the regulation of serum high density lipoproteins in type II diabetes mellitus. J. Clin. Endocrinol. Metab. 65: 183–187, 1987.
 191. Kennedy, A. L., T. R. J. Lappin, T. D. Lavery, D. R. Hadden, J. A. Weaver, and D. A. D. Montgomery. Relation of high‐density lipoprotein cholesterol concentration to type of diabetes and its control. BMJ 2: 1191–1194, 1978.
 192. Kern, P. A.. Lipoprotein lipase and hepatic lipase. Curr. Opin. Lipidol. 2: 162–169, 1991.
 193. Kesaniemi, Y. A., J. L. Witztum, and U. P. Steinbrecher. Receptor‐mediated catabolism of low density lipoprotein in man. Quantitation using glucosylated low density lipoprotein. J. Clin. Invest. 71: 950–959, 1983.
 194. Khan, B., H. G. Wilcox, and M. Heimberg. Cholesterol is required for secretion of very‐low‐density lipoprotein by rat liver. Biochem. J. 259: 807–816, 1989.
 195. Khan, B. V., T. V. Fungwe, H. G. Wilcox, and M. Heimberg. Cholesterol is required for the secretion of the very‐low‐density lipoprotein: in vivo studies. Biochim. Biophys. Acta 1044: 297–304, 1990.
 196. Kissebah, A. H.. Low density lipoprotein metabolism in non‐insulin‐dependent diabetes mellitus. Diabetes Metab. Rev. 3: 619–651, 1987.
 197. Kissebah, A. H., A. Alfarsi, and P. W. Adams. Integrated regulation for very low density lipoprotein triglyceride and apolipoprotein‐B kinetics in man: normolipidemic subjects, familial hypertriglyceridemia and familial combined hyperlipidemia. Metabolism 20: 856–868, 1981.
 198. Kissebah, A. H., S. Alfarsi, P. W. Adams, M. Seed, J. Folkard, and V. Wynn. Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglycerideaemia. Atherosclerosis 24: 199–218, 1976.
 199. Kissebah, A. H., S. Alfarsi, and D. J. Evans. Low density lipoprotein metabolism in familial combined hyperlipidemia: mechanism of the multiple lipoprotein phenotypic expression. Arteriosclerosis 4: 614–624, 1984.
 200. Kissebah, A. H., S. Alfarsi, D. J. Evans, and P. W. Adams. Integrated regulation of very‐low‐density lipoprotein triglyceride and apolipoprotein‐B kinetics in non‐insulin‐dependent diabetes mellitus. Diabetes 31: 217–225, 1982.
 201. Klein, R. L., T. J. Lyons, and M. F. Lopes‐Virella. Interaction of very‐low‐density lipoprotein isolated from type 1 (insulin‐dependent) diabetic subjects with human monocyte‐derived macrophages. Metabolism 38: 1108–1114, 1989.
 202. Knott, T. J., R. J. Pease, L. M. Powell, S. C. Wallis, J. Rall, T. L. Innerarity, B. Blackhart, W. H. Taylor, Y. Marcel, R. Milne, D. Johnson, M. Fuller, A. J. Lusis, B. J. McCarthy, R. W. Mahley, B. Levy‐Wilson, and J. Scott. Complete protein sequence and identification of structural domains of human apolipoprotein B. Nature 323: 734–738, 1986.
 203. Komaromy, M., S. Azhar, and A. D. Cooper. Chinese hamster ovary cells expressing a cell surface‐anchored form of hepatic lipase. Characterization of low density lipoprotein and chylomicron remnant uptake and selective uptake of high density lipoprotein‐cholesteryl ester. J. Biol. Chem. 271: 16906–16914, 1996.
 204. Kostner, G. M., G. Knipping, J. E. Groener, R. Zechner, and H. Dieplinger. The role of LCAT and cholesteryl ester transfer proteins for the HDL and LDL structure and metabolism. Adv. Exp. Med. Biol. 210: 79–86, 1987.
 205. Kosykh, V. A., S. N. Preobrzhensky, I. V. Fuki, O. E. Zaikina, V. P. Tsibulsky, V. S. Repin, and V. N. Smirnov. Cholesterol can stimulate secretion of apolipoprotein B by cultured human hepatocytes. Biochim. Biophys. Acta 836: 385–389, 1985.
 206. Kowal, R. C., J. Herz, K. H. Weisgraber, R. W. Mahley, M. S. Brown, and J. L. Goldstein. Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor‐related protein. J. Biol. Chem. 265: 10771–10779, 1990.
 207. Kraemer, F. B.. Diabetes and lipoprotein receptors. Diabetes Metab. Rev. 3: 591–618, 1987.
 208. Kraemer, F. B., Y. Chen, R. D. Lopez, and G. M. Reaven. Effects of noninsulin‐dependent diabetes mellitus on the uptake of very low density lipoproteins by thioglycolate‐elicited mouse peritoneal macrophages. J. Clin. Endocrinol. Metab. 61: 335–342, 1985.
 209. Krauss, R. M., and A. V. Nichols. Metabolic interrelationships of HDL subclasses. Adv. Exp. Med. Biol. 201: 17–27, 1986.
 210. Krolewski, A. S., E. L. Kosinski, J. H. Warram, O. S. Leland, E. J. Busick, A. C. Asmal, L. I. Rand, A. R. Christlieb, R. F. Bradley, and C. R. Kahn. Magnitude and determinants of coronary artery disease in juvenile‐onset, insulin dependent diabetes mellitus. Am. J. Cardiol. 59: 750–755, 1987.
 211. Kroon, P. A., J. A. De Martino, G. M. Thompson, and Y. Chao. Molecular cloning of partial cDNAs for rabbit liver apolipoprotein B and the regulation of its mRNA levels by dietary cholesterol. Proc. Natl. Acad. Sci. U.S.A. 83: 5071–5075, 1986.
 212. Krul, E. S., M. J. Tikkanen, T. G. Cole, J. M. Davie, and G. Schonfeld. Roles of apolipoproteins B and E in the cellular binding of very low density lipoproteins. J. Clin. Invest. 75: 361–369, 1985.
 213. Kuksis, A., J. J. Myher, and K. Geher. Decreased plasma phosphatidylcholine/free cholesterol ratio as an indicator of risk for ischemic vascular disease. Arteriosclerosis 2: 296–302, 1982.
 214. Kushwaha, R. S., C. A. McMahan, G. E. Mott, K. D. Carey, C. A. Reardeon, G. S. Getz, and J. McGill. Influence of dietary lipids on hepatic mRNA levels of proteins regulating plasma lipoproteins in baboons with high and low levels of large high density lipoproteins. J. Lipid Res. 32: 1929–1940, 1991.
 215. Kushwaha, R. S., and W. R. Hazzard. Catabolism of very low density lipoproteins in the rabbit. Effect of changing composition and pool size. Biochim. Biophys. Acta 528: 176–189, 1978.
 216. La Ville, A., R. Moshy, P. R. Turner, N. E. Miller, and B. Lewis. Inhibition of cholesterol synthesis reduces low‐density‐lipoprotein apoprotein B production without decreasing very‐low‐density‐lipoprotein B synthesis in rabbits. Biochem. J. 219: 321–323, 1984.
 217. Laakso, M., K. Pyorala, H. Sarlund, and E. Voutilainen. Lipid and lipoprotein abnormalities associated with coronary heart disease in patients with insulin‐dependent diabetes mellitus. Arteriosclerosis 6: 679–684, 1986.
 218. Laakso, M., H. Sarlund, and L. Mykkanen. Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance. Arteriosclerosis 10: 223–231, 1990.
 219. Landschulz, K. T., R. K. Pathak, A. Rigotti, M. Krieger, and H. H. Hobbs. Regulation of scavenger receptor, class B, type I, a high density lipoprotein receptor, in liver and steroidogenic tissues of the rat. J. Clin. Invest 98: 984–995, 1996.
 220. Lawson, S. W., K. Grant, A. Higuchi, K. Hospattankar, N. Lackner, N. Lee, and H. B. Brewer, Jr.. Human liver aplipoprotein B‐100 cDNA: complete nucleic acid and derived amino acid sequence. Proc. Natl. Acad. Sci. U.S.A. 83: 8142–8146, 1986.
 221. Le, N., J. C. Gibson, and H. N. Ginsberg. Independent regulation of plasma apolipoprotein CII and CIII concentrations in very low density and high density lipoproteins: implications for the regulation of the catabolism of these lipoproteins. J. Lipid Res. 29: 669–677, 1988.
 222. Leiper, J. M., G. B. Harrison, J. D. Bayliss, J. Scott, and R. J. Pease. Systematic expression of the complete coding sequence of apoB‐100 does not reveal transmembrane determinants. J. Lipid Res. 37: 2215–2231, 1996.
 223. Leroy, A., J. Dallongeville, and J. C. Fruchart. Apolipoprotein A‐I‐containing lipoproteins and atherosclerosis. Curr. Opin. Lipidol. 6: 281–285, 1995.
 224. Lewis, G. F.. Fatty acid regulation of very low density lipoprotein (VLDL) production. Curr. Opin. Lipidol 8: 146–153, 1997.
 225. Lewis, G. F., K. D. Uffelman, L. W. Szeto, and G. Steiner. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes 42: 833–842, 1993.
 226. Lewis, G. F., K. D. Uffelman, L. W. Szeto, B. Weller, and G. Steiner. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J. Clin. Invest. 95: 158–166, 1995.
 227. Li, W., M. Tanimura, C. Luo, S. Datta, and L. Chan. The apolipoprotein multigene family: biosynthesis, structure, structure‐function relationships, and evolution. J. Lipid Res, 29: 245, 1988.
 228. Li, W. W., M. M. Dammerman, J. D. Smith, S. Metzger, J. L. Breslow, and T. Leff. Common genetic variation in the promoter of the human apo CIII gene abolishes regulation by insulin and may contribute to hypertriglyceridemia. J. Clin. Invest. 96: 2601–2605, 1995.
 229. Lin, M. C., C. C. Arbeeny, K. Bergquist, B. Kienzle, D. A. Gordon, and J. R. Wetterau. Cloning and regulation of hamster microsomal triglyceride transfer protein. The regulation is independent from that of other hepatic and intestinal proteins which participate in the transport of fatty acids and triglycerides. J. Biol. Chem. 269: 29138–29145, 1994.
 230. Lin, M. C., D. Gordon, and J. R. Wetterau. Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression. J. Lipid Res. 36: 1073–1081, 1995.
 231. Lindgren, F. T., L. D. Jensen, and F. T. Hatch. The isolation and quantitative analysis of serum lipoproteins. In: Blood Lipids and Lipoproteins. New York: Wiley, 1972, p. 181–197.
 232. Little, J. A., and P. W. Connelly. Familial hepatic lipase deficiency. Adv. Exp. Med. Biol. 201: 253–260, 1986.
 233. Liu, L., and D. L. Severson. Myocardial lipoprotein lipase activity: regulation by diabetes and fructose‐induced hypertriglyceridemia. Can. J. Physiol. Pharmacol. 73: 369–377, 1995.
 234. Liu, L., and D. L. Severson. Regulation of myocardial lipoprotein lipase activity by diabetes and thyroid hormones. Can. J. Physiol. Pharmacol. 72: 1259–1264, 1994.
 235. Lopes‐Virella, M. F., R. L. Klein, T. J. Lyons, H. C. Stevenson, and J. L. Witztum. Glycosylation of low‐density lipoprotein enhances cholesteryl esterol synthesis in human monocyte‐derived macrophages. Diabetes 37: 550–557, 1988.
 236. Lopes‐Virella, M. F., H. J. Wohltmann, C. B. Loadholt, and M. G. Buse. Plasma lipids and lipoproteins in young insulin‐dependent diabetic patients: relationship with control. Diabetologia 21: 216–223, 1981.
 237. Lopes‐Virella, M. F. L., P. G. Stone, and J. A. Colwell. Serum high density lipoprotein in diabetic patients. Diabetologia 13: 285–291, 1977.
 238. Lyons, T. J., J. W. Baynes, J. S. Patrick, J. A. Colwell, and M. F. Lopes‐Virella. Glycosylation of low density lipoprotein in patients with type 1 (insulin‐dependent) diabetes: correlation with other parameters of glycaemic control. Diabetologia 29: 685–689, 1986.
 239. Lyons, T. J., and A. J. Jenkins. Lipoprotein glycation and its metabolic consequences. Curr. Opin. Lipidol. 8: 174–180, 1997.
 240. Maeda, N., H. Li, D. Lee, P. Oliver, S. H. Quarfordt, and J. Osada. Targeted disruption of the apolipoprotein C‐III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. J. Biol. Chem. 269: 23610–23616, 1994.
 241. Mahley, R. W.. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240: 622–630, 1988.
 242. Mahley, R. W., T. L. Innerarity, S. C. J. Rall, and K. H. Weisgraber. Plasma lipoproteins: apolipoprotein structure and function. J. Lipid. Res. 25: 1277–1294, 1984.
 243. Mahley, R. W., and S. C. Rall. Type III hyperlipoproteinemia. In: The Metabolic Basis of Inherited Disorders, edited by C. R. Servier, A. L. Bendit, W. S. Sly, and D. Valle. New York: McGraw‐Hill, 1989, p. 1195–1214.
 244. Marzetta, C. A., D. M. Foster, and J. D. Brunzell. Conversion of plasma VLDL and IDL precursors into various LDL subpopulations using density gradient ultracentrifugation. J. Lipid Res. 31: 975–984, 1990.
 245. Marzetta, C. A., F. L. Johnson, L. A. Zech, D. M. Foster, and L. L. Rudel. Metabolic behavior of hepatic VLDL and plasma LDL apoB‐100 in African green monkeys. J. Lipid Res. 30: 357–370, 1989.
 246. Mattock, M. B., A. M. Salter, J. H. Fuller, T. Omer, R. E. Gohari, S. D. Redmond, and H. Keen. High density lipoprotein subfractions in insulin‐dependent diabetic and normal subjects. Atherosclerosis 45: 67–79, 1982.
 247. Melish, J., N. Le, H. Ginsberg, D. Steinberg, and W. V. Brown. Dissociation of triglyceride and apoprotein‐B production in very low density lipoproteins. Am. J. Physiol. 239 (Endocrinol. Metab. 2): E354–E362, 1980.
 248. Miller, G. J., and N. E. Miller. Plasma high density lipoprotein concentration and development of ischaemic heart disease. Lancet I: 16–19, 1975.
 249. Miller, N. E., D. S. Thelle, O. H. Forde, and O. D. Mjos. The Tromso heart study. High density lipoprotein and coronary heart disease: a prospective case control study. Lancet I: 965–968, 1977.
 250. Moberly, J. B., T. G. Cole, D. H. Alpers, and G. Schonfeld. Oleic acid stimulation of apolipoprotein B secretion from HepG2 and Caco‐2 cells occurs post‐transcriptionally. Biochim. Biophys. Acta 1042: 70–80, 1990.
 251. Mokuno, H., S. Brady, L. Kotite, J. Herz, and R. J. Havel. Effect of the 39‐kDa receptor‐associated protein on the hepatic uptake and endocytosis of chylomicron remnants and low density lipoproteins in the rat. J. Biol. Chem. 269: 13238–13243, 1994.
 252. Mulder, M., P. Lombardi, H. Jansen, T. J. C. van Berkel, R. R. Frants, and L. M. Havekes. Heparan sulphate proteoglycans are involved in the lipoprotein lipase‐mediated enhancement of the cellular binding of very low density lipoproteins. Biochem. Biophys. Res. Commun. 185: 582–587, 1992.
 253. Muller, D. L., C. D. Saudek, and D. Applebaum‐Bowden. Hepatic triglyceride lipase in diabetic dogs. Metabolism 34: 251–254, 1997.
 254. Muller, G., E. A. Dearey, and J. Punter. The sulphonylurea drug, glimepiride, stimulates release of glycosylphosphatidylinositol‐anchored plasma‐membrane proteins from 3T3 adipocyte. Biochemistry 289: 509–521, 1993.
 255. Muller, G., E. M. Wetekam, C. Jung, and W. Bandlow. Membrane association of lipoprotein lipase and a cAMP‐binding ectoprotein in rat adipocytes. Biochemistry 33: 12149–12159, 1994.
 256. Murase, T., and S. Inoue. Hepatic triglyceride lipase is not an insulin‐dependent enzyme in rats. Metabolism 34: 531–534, 1985.
 257. Nakai, T., S. Yamada, T. Tamai, T. Kobayashi, T. Hayashi, and R. Takeda. The effect of streptozotocin diabetes on hepatic triglyceride lipase activity in the rat. Metabolism 28: 30–40, 1979.
 258. Nicoll, A., N. E. Miller, and B. Lewis. High density lipoportein metabolism. In: Advances in Lipid Research. New York: Academic, 1980, p. 54.
 259. Nikkila, E. A.. Very low density lipoprotein triglyceride metabolism in diabetes. In: Atherosclerosis, edited by R. W. James and D. Pometta. Basel: Karger, 1985, p. 44–62.
 260. Nikkila, E. A., and P. Hormila. Serum lipids and lipoprotein in insulin‐treated diabetes: demonstration of increased high density lipoprotein concentration. Diabetes 27: 1078–1086, 1978.
 261. Nikkila, E. A., J. K. Huttunen, and C. Enholm. Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus: relationship to plasma triglyceride metabolism. Diabetes 26: 11–21, 1977.
 262. Nikkila, E. A., and M. Kekki. Plasma triglyceride transport kinetics in diabetes mellitus. Metabolism 22: 1–22, 1973.
 263. Nishigaki, I., M. Hagihara, H. Tsunekawa, M. Maseki, and K. Yagi. Lipid peroxide levels in serum lipoprotein fractions of diabetic patients. Biochem. Med. 25: 373–378, 1981.
 264. Obunike, J. C., P. Sivaram, L. Paka, M. G. Low, and I. J. Goldberg. Mechanisms of lipoprotein lipase degradation by adipocytes: receptor associated protein (RAP) sensitive and proteoglycan mediated pathways. J. Lipid. Res. 37: 2439–2449, 1996.
 265. Ogbonna, G., A. Theriault, and K. Adeli. Hormonal regulation of human apolipoprotein E gene expression in HepG2 cells. Int. J. Biochem. 25: 635–640, 1993.
 266. Olefsky, J. M., J. W. Farquhar, and G. M. Reaven. Reappraisal of the role of insulin in hypertriglyceridemia. Am. J. Med. 57: 551–560, 1974.
 267. Olivecrona, G., and T. Olivecrona. Triglyceride lipases and atherosclerosis. Curr. Opin. Lipidol. 6: 291–305, 1995.
 268. Olivecrona, T., and G. Olivecrona‐Bengtsson. Lipoprotein lipase from milk—the model enzyme in lipoprotein lipase research. In: Lipoprotein Lipase, edited by J. Borensztajn. Chicago: Evener, 1987, p. 15–58.
 269. Oliver, J. D., and M. P. Rogers. Stimulation of lipoprotein lipase synthesis by refeeding, insulin and dexamethasone. Biochem. J. 292: 525–530, 1993.
 270. Oliver, M. F., J. A. Heady, and J. N. Morris. Report from the committee of principal investigators: a cooperative trial in the primary prevention of ischaemic heart disease using clofibrate. Br. Heart. J. 40: 1069–1118, 1978.
 271. Olofsson, S. O., G. Bjursell, K. Bostrom, P. Carlsson, J. Elovson, A. A. Protter, M. A. Rueben, and G. Bondjers. Apolipoprotein B: structure, biosynthesis and role in the lipoprotein assembly process. Atherosclerosis 68: 1–17, 1987.
 272. O'Looney, P., M. V. Maten, and G. V. Vahouny. Insulin‐mediated modifications of myocardial lipoprotein lipase and lipoprotein metabolism. J. Biol. Chem. 258: 12994–13002, 1983.
 273. Oram, J. F., J. P. Slotte, M. Aviram, P. B. Duell, D. L. Graham, and E. L. Bierman. High density lipoprotein receptor‐mediated transport of excess cholesterol from cells. In: High Density Lipoproteins and Atherosclerosis II, edited by N. E. Miller. Amsterdam: Elsevier, 1989, p. 225–232.
 274. Ostlund, R. E., Jr., C. F. Semenhovich, and K. B. Schechtman. Quantitative relationship between plasma lipids and glycohemoglobin in type I diabetes. Diabetes Care 12: 332–336, 1989.
 275. Packard, C. J., M. J. Caslake, and J. Shepherd. Effects of fenofibrate on receptor‐mediated and receptor‐independent low density lipoprotein catabolism in hypertriglyceridaemic subjects. Monogr. Atheroscler. 13: 142–144, 1985.
 276. Packard, C. J., R. J. Clegg, M. H. Dominiczak, A. R. Lorimer, and J. Shepherd. Effects of bezafibrate on apolipoprotein B metabolism in type III hyperlipoproteinemic subjects. J. Lipid Res. 27: 930–938, 1986.
 277. Packard, C. J., A. Munro, A. R. Lorimer, A. M. Gotto, and J. Shepherd. Metabolism of apolipoprotein B in large triglyceride‐rich very low density lipoproteins of normal and hypertriglyceridemic subjects. J. Clin. Invest. 74: 2178–2192, 1984.
 278. Palade, G.. Intracellular aspects of the process of protein synthesis. Science 189: 347–358, 1975.
 279. Pape, M. E., C. K. Castle, R. W. Murray, G. M. Funk, C. E. Hunt, K. R. Marotti, and G. W. Melchior. Apo B metabolism in the cynomolgus monkey: evidence for post‐transcriptional regulation. Biochim. Biophys. Acta 1086: 326–334, 1991.
 280. Parkes, J. G., P. Chan, and D. M. Goldberg. Secretion of triglyceride lipase from rat hepatocytes in culture: modulation by insulin and phenobarbital. Biochem. Cell. Biol. 64: 1147–1152, 1986.
 281. Patsch, W., S. Franz, and G. Schonfeld. Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J. Clin. Invest. 71: 1161–1174, 1983.
 282. Patsch, W., A. M. Gotto, Jr., and J. R. Patsch. Effects of insulin on lipoprotein secretion in rat hepatocyte cultures. The role of the insulin receptor. J. Biol. Chem. 261: 9603–9606, 1986.
 283. Patten, R. L.. The reciprocal regulation of lipoprotein lipase activity and hormone‐sensitive lipase activity in rat adipocytes. J. Biol. Chem. 245: 5577–5584, 1970.
 284. Pease, R. J., G. B. Harrison, and J. Scott. Cotranslational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum. Nature 353: 448–450, 1991.
 285. Peinado‐Onsurbe, J., C. Soler, M. Soley, M. Llobera, and I. Ramirez. Lipoprotein lipase and hepatic lipase activities are differentially regulated in isolated hepatocytes from neonatal rats. Biochem. Biophys. Acta. 1125: 82–89, 1992.
 286. Pietri, A., F. Dunn, and P. Raskin. The effect of improved diabetic control on plasma lipid and lipoprotein levels: a comparison of conventional therapy and continuous subcutaneous insulin infusion. Diabetes 29: 1001–1005, 1980.
 287. Pietri, A. O., F. L. Dunn, S. M. Grundy, and P. Raskin. The effect of continuous subcutaneous insulin infusion on very low‐density lipoprotein triglyceride metabolism in type I diabetes mellitus. Diabetes 32: 75–81, 1983.
 288. Pitmann, R. C., T. P. Knecht, M. S. Rosenbaum, and C. A. Taylor, Jr.. A non‐endocytic mechanism for the selective uptake of high density lipoprotein‐associated cholesterol esters. J. Biol. Chem. 262: 2443–2451, 1987.
 289. Plump, A. S., J. D. Smith, T. Hayek, K. Aalto‐Setala, A. Walsh, J. G. Verstuyft, E. M. Rubin, and J. L. Breslow. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E‐deficient mice created by homologous recombinaiton in ES cells. Cell 71: 343–353, 1992.
 290. Pollare, T., B. Vessby, and H. Lithell. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler. Thromb. 11: 1192–1203, 1991.
 291. Powell, L. M., S. C. Wallis, R. J. Pease, Y. H. Edwards, T. J. Knott, and J. Scott. A novel form of tissue‐specific RNA processing produces apolipoprotein‐B48 in intestine. Cell 50: 831–840, 1987.
 292. Previato, L., C. L. Parrott, F. S. Santamarina, and H. J. Brewer. Transcriptional regulation of the human lipoprotein lipase gene in 3T3–L1 adipocytes. J. Biol. Chem. 266: 18958–18963, 1991.
 293. Puchois, P., A. Kandoussi, P. Fievet, J. L. Fourrier, M. Bertrand, E. Koren, and J. C. Fruchart. Apolipoprotin A‐I‐containing lipoproteins in coronary artery disease. Atherosclerosis 68: 35–40, 1987.
 294. Pullinger, C. R., and G. F. Gibbons. Effects of hormones and pyruvate on the rates of secretion of very‐low‐density lipoprotein triacylglycerol and cholesterol by rat hepatocytes. Biochim. Biophys. Acta 833: 44–51, 1985.
 295. Pullinger, C. R., J. D. North, B. Teng, V. A. Rifici, A. E. Ronhild de Brito, and J. Scott. The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half‐life. J. Lipid Res. 30: 1065–1076, 1989.
 296. Quarfordt, S., G. Michalopoulos, and B. Schrimer. The effect of human C apolipoproteins on the in vitro hepatic metabolism of triglyceride emulsions in rats. J. Biol. Chem. 257: 14642–14647, 1982.
 297. Rader, D. J., G. Castro, L. A. Zech, J. Fruchart, and H. B. Brewer, Jr.. In vivo metabolism of apolipoprotein A‐I on high density lipoprotein particles LpA‐I and LpA‐I, A‐II. J. Lipid Res. 32: 1849–1859, 1991.
 298. Ranganathan, G., J. M. Ong, A. Yukht, M. Saghizadeh, R. B. Simsolo, A. Pauer, and P. A. Kern. Tissue‐specific expression of human lipoprotein lipase. Effect of the 3′‐untranslated region on translation. J. Biol Chem. 270: 7149–7155, 1995.
 299. Rao, s. N., P. J. Magill, N. E. Miller, and B. Lewis. Plasma high‐density lipoprotein metabolism in subjects with primary hypertrig‐lyceridaemia: altered metabolism of apoproteins AI and AII. Clin. Sci. (Colch.) 59: 359–367, 1980.
 300. Reaven, E. P., and G. M. Reaven. Mechanisms for development of diabetic hypertriglyceridemia in streptozotocin treated rats: effect of diet and duration of insulin deficiency. J. Clin. Invest. 54: 1167–1178, 1974.
 301. Reaven, G. M.. Role of insulin resistance in human disease. Diabetes 37: 1595–1607, 1988.
 302. Reaven, G. M., and Y. Chen. Role of insulin in regulation of lipoprotein metabolism in diabetes. Diabetes Metab. Rev. 4: 639–652, 1988.
 303. Reaven, G. M., Y. Chen, J. Jeppesen, P. Maheux, and R. M. Krauss. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J. Clin. Invest. 92: 141–146, 1993.
 304. Reaven, G. M., and A. Laws. Coronary heart disease in the absence of hypercholesterolaemia. J. Intern. Med. 228: 415–417. 1990.
 305. Reckless, J. P. D., S. Black, and R. V. Brunt. Glycation of very low‐density lipoproteins in diabetes. In: Atherosclerosis. Basel: Karger, 1985, p. 130–133.
 306. Reckless, J. P. D., D. J. Betteridge, P. Wu, B. Payne, and D. J. Galton. 1978. High and low density lipoproteins and the prevalence of vascular disease in diabetes mellitus. BMJ 1: 883–886, 1978.
 307. Ribeiro, A., M. Mangeney, C. Loriette, G. Thomas, D. Pepin, B. Janvier, J. Chambaz, and G. Bereziat. Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes. Biochim. Biophys. Acta 1086: 279–286, 1991.
 308. Rivellese, A., G. Riccardi, G. Romano, R. Giacco, L. Patti, G. Marotta, G. Annuzi, and M. Mancini. Presence of very low density lipoprotein compositional abnormalities in type 1 (insulin‐dependent) diabetic patients: effects of blood glucose optimisation. Diabetologia 31: 884–888, 1988.
 309. Rodrigues, B., J. E. A. Braun, M. Spooner, and D. L. Severson. Regulation of lipoprotein lipase in cardiac myocytes from control and diabetic rat hearts by plasma lipids. Can. J. Physiol. Pharmacol. 70: 1271–1279, 1993.
 310. Rodrigues, B., and D. L. Severson. Acute diabetes does not reduce heparin‐releasable lipoprotein lipase activity in perfused hearts from Wistar‐Kyoto rats. Can. J. Physiol. Pharmacol. 71: 657–661, 1993.
 311. Rosenstock, J., G. L. Vega, and P. Raskin. Effect of intensive diabetes treatment on low‐density lipoprotein apolipoprotein B kinetics in type I diabetes. Diabetes 37: 393–397, 1988.
 312. Rosenstock, J., S. Strowig, S. Cercone, and P. Raskin. Reduction in cardiovascular risk factors with intense diabetes treatment in insulin‐dependent diabetes mellitus. Diabetes Care 10: 729–734, 1987.
 313. Rumsey, S., J. C. Obunike, Y. Arad, R. Deckelbaum, and I. J. Goldberg. Lipoprotein lipase mediated uptake and degradation of low density lipoproteins by fibroblasts and macrophages. J. Clin. Invest. 90: 1504–1512, 1992.
 314. Ruotolo, G., F. Ragogna, P. Micossi, and G. Pozza. Normalization of lipoprotein composition by intraperitoneal insulin in IDDM. Role of increased hepatic lipase activity. Diabetes Care 17: 6–12, 1994.
 315. Ruotolo, G., P. Micossi, G. Galimberti, M. C. Librent, G. Petrella, S. Marcovina, G. Pozza, and B. V. Howard. Effect of intraperitoneal vs. subcutaneous insulin administration on lipoprotein metabolism in type I diabetes. Metabolism 39: 598–604, 1990.
 316. Sato, R., T. Imanaka, A. Takatsuki, and T. Takano. Degradation of newly synthesized apolipoprotein B‐100 in a pre‐Golgi compartment. J. Biol. Chem. 265: 11880–11884, 1990.
 317. Sato, R., T. Imanaka, and T. Takano. The effect of HMG‐CoA reductase inhibitor (CS‐514) on the synthesis and secretion of apolipoproteins B and A‐1 in the human hepatoblastoma Hep G2. Biochim. Biophys. Acta 1042: 36–41, 1990.
 318. Saxena, U., M. G. Klein, and I. J. Goldberg. Identification and characterization of the endothelial cell proteoglycan binding site for lipoprotein lipase. J. Biol. Chem. 266: 17516–17521, 1991.
 319. Saxena, U., M. G. Klein, and I. J. Goldberg. Transport of lipoprotein lipase across endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 88: 2254–2258, 1991.
 320. Saxena, U., L. Witte, and I. J. Goldberg. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids. J. Biol. Chem. 264: 4349–4355, 1989.
 321. Shachter, N. S., T. Ebara, R. Ramakrishnan, G. Steiner, J. Breslow, H. N. Ginsberg, and J. D. Smith. Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein CI. J. Clin. Invest. 98: 846–855, 1996.
 322. Schachter, N. S., T. Hayek, T. Leff, J. D. Smith, D. W. Rosenberg, A. Walsh, R. Ramakrishnan, I. Goldberg, H. N. Ginsberg, and J. L. Breslow. Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice. J. Clin. Invest. 93: 1683–1690, 1994.
 323. Shachter, N. S., T. Leff, J. D. Smith, D. W. Rosenberg, A. Walsh, R. Ramakrishnan, H. N. Ginsberg, and J. L. Breslow. Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice. J. Clin. Invest. 93: 1683–1690, 1994.
 324. Schaefer, E. J.. Clinical, biochemical, and genetic features in familial disorders of high density lipoprotein deficiency. Arteriosclerosis 4: 303–322, 1984.
 325. Schaefer, E. J., D. M. Foster, L. A. Zech, F. T. Lindgren, J. Brewer, and R. I. Levy. The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. J. Clin. Endocrinol. Metab. 57: 262–267, 1983.
 326. Schaefer, E. J., R. E. Gregg, G. Ghiseli, T. M. Forte, J. M. Ordovas, L. A. Zech, and H. B. Brewer, Jr.. Familial apolipoprotein E deficiency. J. Clin. Invest. 78: 1206–1219, 1986.
 327. Schaefer, E. J., L. A. Sech, and L. L. Jenkins. Human apolipoprotein A‐I and A‐II metabolism. J. Lipid Res. 23: 850–862, 1982.
 328. Schekman, R.. Polypeptide translocation: a pretty picture is worth a thousand words. Cell 87: 593–595, 1996.
 329. Scherthander, G., G. M. Kostner, H. Dieplinger, H. Prager, and I. Muhlhauser. Apolipoproteins (A‐I, A‐II, B) Lp(a) lipoprotein and lechithin: cholesterol, acyltransferase activity in diabetes mellitus. Atherosclerosis 49: 277–293, 1973.
 330. Schleicher, E., B. Olgemoller, J. Schon, T. Durst, and O. H. Wieland. Limited nonenzymatic glucosylation of low‐density lipoprotein does not alter its catabolism in tissue culture. Biochim. Biophys. Acta 846: 226–233, 1985.
 331. Schneider, W. J., P. T. Kovanen, M. S. Brown, J. L. Goldstein, G. Utermann, W. Weber, R. J. Havel, L. Kotite, J. P. Kane, T. L. Innerarity, and R. W. Mahley. Familial dysbetalipoproteinemia. Abnormal binding of mutant apopprotein E to low density lipoprotein receptors of human fibroblasts and membranes from liver and adrenal of rats, rabbits and cows. J. Clin. Invest. 68: 1075–1085, 1981.
 332. Scott, J.. The molecular and cell biology of apolipoprotein‐B. Mol. Biol. Med. 6: 65–80, 1989.
 333. Segrest, J. P., M. K. Jones, V. K. Mishra, G. M. Anantharamaiah, and D. W. Garber. ApoB‐100 has a pentapartite structure composed of three amphipathic alpha‐helical domains alternating with two amphipathic beta‐strand domains. Detection by the computer program LOCATE. Arterioscler. Thromb. 14: 1674–1685, 1994.
 334. Sehayek, E., and S. Eisenberg. Mechanisms of inhibition by apolipoprotein C of apolipoprotein E‐dependent cellular metabolism of human triglyceride‐rich lipoproteins through the low density lipoprotein receptor pathway. J. Biol. Chem. 266: 18259–18267, 1991.
 335. Sehayek, E., U. Lewin‐Velvert, T. Chajek‐Shaul, and S. Eisenberg. Lipolysis exposes unreactive endogenous apolipoprotein E‐3 in human and rat plasma very low density lipoprotein. J. Clin. Invest. 88: 553–560, 1991.
 336. Semenkovich, C. F., M. Wims, L. Noe, J. Etienne, and L. Chan. Insulin regulation of lipoprotein lipase activity in 3T3–L1 adipocytes is mediated at posttranscriptional and posttranslational levels. J. Biol. Chem. 264: 9030–9038, 1989.
 337. Shames, D. M., and R. J. Havel. De novo production of low density lipoproteins: fact or fancy. J. Lipid Res. 32: 1099–1112, 1991.
 338. Shelburne, F., J. Hanks, W. Meyers, and S. Quarfordt. Effect of apoproteins on hepatic uptake of triglyceride emulsions in the rat. J. Clin. Invest. 65: 652–659, 1980.
 339. Shepherd, J., C. J. Packard, S. Bicker, T. D. Lawrie, and H. G. Morgan. Cholestyramine promotes receptor‐mediated low‐density‐lipoprotein catabolism. N. Engl. J. Med. 302: 1219–1222, 1980.
 340. Shepherd, J., C. J. Packard, J. R. Patsch, A. M. Gotto, Jr., and D. O. Taunton. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J. Clin. Invest. 63: 858–867, 1979.
 341. Shimada, M., S. Ishibashi, T. Gotoda, M. Kawamura, K. Yamamoto, T. Inaba, K. Harada, J. Ohsuga, S. Perry, Y. Yazaki, and N. Yamada. Overexpression of human lipoprotein lipase protects diabetic transgenic mice from diabetic hypertriglyceridemia and hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 15: 1688–1694, 1995.
 342. Sigurdsson, G., A. Nicoll, and B. Lewis. Metabolism of very low density lipoproteins in hyperlipidemia: studies of apolipoprotein B kinetics in man. Eur. J. Clin. Invest. 6: 167–177, 1976.
 343. Simsolo, R. B., J. M. Ong, B. Saffari, and P. A. Kern. Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue. J. Lipid. Res. 33: 89–95, 1992.
 344. Sivaram, P., S. Y. Choi, L. K. Curtiss, and I. J. Goldberg. An amino‐terminal fragment of apolipoprotein B binds to lipoprotein lipase and may facilitate its binding to endothelial cells. J. Biol. Chem. 269: 9409–9412, 1994.
 345. Sivaram, P., M. G. Klein, and I. J. Goldberg. Characterization of a non‐proteoglycan lipoprotein lipase binding protein from endothelial cells. J. Biol. Chem. 267: 16517–16522, 1992.
 346. Skowronski, R., J. Pietarinen, M. Chang, A. M. Coulston, and Y. Chen. Is non‐insulin dependent diabetes mellitus associated with an increase in postprandial retinyl ester concentration? Diabetes 39 (Suppl. 1): 63A, 1990.
 347. Slavin, B. G., J. M. Ong, and P. A. Kern. Hormonal regulation of hormone‐sensitive lipase activity and mRNA levels in isolated rat adipocytes. J. Lipid Res. 35: 1535–1541, 1994.
 348. Smith, H. C.. Apolipoprotein B mRNA editing: the sequence to the event. Semin. Cell. Biol. 4: 267–278, 1993.
 349. Sorci‐Thomas, M., M. D. Wilson, F. L. Johnson, D. L. Williams, and L. L. Rude. Studies on the expression of genes encoding apolipoproteins B100 and B48 and the low density lipoprotein receptor in nonhuman primates. J. Biol. Chem. 264: 9039–9045, 1989.
 350. Sosenko, J. M., J. L. Breslow, and O. S. Miettinen. Hyperglycemia and plasma lipid levels: a prospective study of young insulin‐dependent diabetic patients. N. Engl. J. Med. 302: 650–654, 1980.
 351. Sparks, C. E., T. L. Phung, and M. Bolognino. Insulin‐mediated inhibition of apolipoprotein B secretion requires an intracellular trafficking event and phosphatidylinositol 3‐kinase activation: studies with brefeldin A and wortmannin in primary cultures of rat hepatocytes. Biochem. J. 313: 567–574, 1996.
 352. Sparks, C. E., J. D. Sparks, M. Bolognino, A. Salhanick, P. S. Strumph, and J. M. Amatruda. Insulin effects on apolipoprotein B lipoprotein synthesis and secretion by primary cultures of rat hepatocytes. Metabolism 35: 1128–1135, 1986.
 353. Sparks, J. D., and C. E. Sparks. Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes. J. Biol. Chem. 265: 8854–8862, 1990.
 354. Sparks, J. D., and C. E. Sparks. Insulin regulation of triacylglycerolrich lipoprotein synthesis and secretion. Biochim. Biophys. Acta 1215: 9–32, 1994.
 355. Sparks, J. D., and C. E. Sparks. Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion. Biochem. Biophys. Res. Commun. 205: 417–422, 1994.
 356. Sparks, J. D., R. Zolfaghari, C. E. Sparks, H. C. Smith, and E. A. Fisher. Impaired hepatic apolipoprotein B and E translation in streptozotocin diabetic rats. J. Clin. Invest. 89: 1418–1430, 1992.
 357. Spector, A. A., S. N. Mathur, and T. L. Kaduce. Role of acylcoenzyme A: cholesterol O‐acyltransferase in cholesterol metabolism. Prog. Lipid Res. 18: 31–53, 1979.
 358. Stalenhof, A. F. H., P. N. M. Damacker, J. A. Lutterman, and A. van't Laar. Apolipoprotein C in type 2 (non‐insulin‐dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 22: 489–491, 1982.
 359. Stein, O., Y. Dabach, G. Hollander, M. Ben‐Naim, K. Oette, and Y. Stein. Effects of interactions of apolipoprotein A‐II with apolipoproteins A‐I or A‐IV on [3H]cholesterol efflux and uptake in cell culture. Biochim. Biophys. Acta 1257: 174–180, 1995.
 360. Steinbrecher, U., and J. L. Witztum. Glucosylation of low‐density lipoproteins on an extent comparable to that seen in diabetes shows their catabolism. Diabetes 33: 130–134, 1984.
 361. Steiner, G., and G. F. Lewis. Hyperinsulinemia and triglyceriderich lipoproteins. Diabetes 45: S24–S26, 1996.
 362. Stralfors, P., and R. C. Honnor. Insulin‐induced dephosphorylation of hormone‐sensitive lipase. Correlation with lipolysis and cAMP‐dependent protein kinase activity. Eur. J. Biochem. 182: 379–385, 1989.
 363. Streicher, R., J. Kotzka, D. Muller‐Wieland, G. Siemeister, M. Munck, H. Avci, and W. Krone. SREBP‐1 mediates activation of the low density lipoprotein receptor promoter by insulin and insulin‐like growth factor‐I. J. Biol. Chem. 271: 7128–7133, 1996.
 364. Strobl, W., K. Widhalm, and E. Schober. Apolipoproteins and lipoproteins in children with type I diabetes: relation to glycosylated serum protein and HbA1. Acta Paediatr. Scand. 74: 966–971, 1985.
 365. Suter, S. L., G. B. Nolan, J. Wallace, L. Gumbiner, and J. M. Olefsky. Metabolic effects of new oral hypoglycemic agent CS‐045 in NIDDM subjects. Diabetes Care 15: 193–203, 1992.
 366. Suzuki, N., S. Oikawa, S. Hori, Y. Fujii, E. Sakuma, H. Kotake, K. Namai, K. Yoshie, and Y. Gotto. Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non‐insulin‐dependent diabetes with type IIa hyperlipoproteinemia. Metabolism 38: 225–229, 1989.
 367. Syvanne, M., M. Ahola, S. Lahdenpera, J. Kahri, T. Kuusi, and K. S. Virtanen. High density lipoprotein subfractions in non‐insulin‐dependent diabetes mellitus and coronary artery disease. J. Lipid Res. 36: 573–582, 1995.
 368. Syvanne, M., J. Kahri, K. S. Virtanen, and M. Taskinen. HDLs containing apolipoproteins A‐I and A‐II (LpA‐I:A‐II) as markers of coronary artery disease in men with non‐insulin‐dependent diabetes mellitus. Circulation 92: 364–370, 1995.
 369. Sztalryd, C., M. Komaromy, and F. B. Kraemer. Overexpression of hormone‐sensitive lipase prevents triglyceride accumulation in adipocytes. J. Clin. Invest. 95: 2652–2661, 1995.
 370. Sztalryd, C., and F. B. Kraemer. Regulation of hormone‐sensitive lipase in streptozotocin‐induced diabetic rats. Metabolism 44: 1391–1396, 1995.
 371. Tall, A. R.. Plasma lipid transfer proteins. J. Lipid Res. 27: 361–367, 1986.
 372. Tall, A. R., D. Sammett, G. M. Vita, R. Deckelbaum, and T. Olivecrona. Lipoprotein lipase enhances the cholesteryl ester transfer protein‐mediated transfer on cholesteryl esters from high density lipoproteins to very low density lipoproteins. J. Biol. Chem. 259: 9587–9594, 1984.
 373. Tall, A. R., and D. M. Small. Plasma high density lipoprotein. N. Engl. J. Med. 299: 1232–1236, 1978.
 374. Talmud, P. J., and S. E. Humphries. Apolipoprotein CIII gene variation and dyslipidemia. Curr. Opin. Lipidol. 8: 154–158, 1997.
 375. Tan, C. E., L. Foster, M. J. Caslake, D. Bedford, T. D. Watson, M. McConnell, C. J. Packard, and J. Shepherd. Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. Arterioscler. Thromb. Vasc. Biol. 15: 1839–1848, 1995.
 376. Taskinen, M., W. F. Beltz, I. Harper, R. M. Fields, G. Schonfeld, S. M. Grundy, and B. V. Howard. The effects of NIDDM on very‐low‐density lipoprotein triglyceride and apolipoprotein B metabolism: studies before and after sulfonylurea therapy. Diabetes 35: 1268–1277, 1986.
 377. Taskinen, M.. Hyperlipidaemia in diabetes. Baillieres Clin. Endocrinol. Metab. 4: 743–775, 1990.
 378. Taskinen, M., J. Kahri, V. Koivisto, J. Sheperd, and C. J. Packard. Metabolism of HDL apolipoprotein A‐I and A‐II in type 1 (insulin‐dependent) diabetes mellitus. Diabetologia 35: 347–356, 1992.
 379. Taskinen, M., T. Kuusi, E. Helve, E. A. Nikkila, and H. Uki‐Jarvinen. Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin‐dependent diabetes. Atherosclerosis 8: 168–177, 1988.
 380. Taskinen, M., T. Kuusi, and E. A. Nikkila. Regulation of HDL and its subfractions in chronically insulin‐treated patients with type I diabetes. In: Diabetes, Obesity and Hyperlipidemias, edited by G. Crepaldi. Amsterdam: Elsevier, 1985, p. 251–259.
 381. Taskinen, M.. Lipoprotein lipase in diabetes. Diabetes Metab. Rev. 3: 551–570, 1987.
 382. Taskinen, M., E. A. Nikkila, T. Kuusi, and K. Harno. Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus: relationship to plasma triglyceride metabolism. Diabetologia 22: 46–50, 1982.
 383. Taskinen, M., E. A. Nikkila, M. Valimaki, T. Sane, T. Kuusi, Y. A. Kesaniemi, and R. Ylikahri. Alcohol‐induced changes in serum lipoproteins and in their metabolism. Am. Heart J. 2: 458–464, 1987.
 384. Taskinen, M., C. J. Packard, and J. Shepherd. Effect of insulin therapy on metabolic fate of apolipoprotein B‐containing lipoproteins in NIDDM. Diabetes 39: 1017–1027, 1990.
 385. Tavanger, K., Y. Murata, M. E. Pedersen, J. F. Goers, A. R. Hoffman, and F. B. Kraemer. Regulation of lipoprotein lipase in the diabetic rat. J. Clin. Invest. 90: 1672–1678, 1992.
 386. Teng, B., A. D. Sniderman, A. K. Soular, and G. R. Thompson. Metabolic basis of hyperapobetalipoproteinemia: turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia. J. Clin. Invest. 77: 663–672, 1986.
 387. Theriault, A., R. Cheung, and K. Adeli. Expression of apolipoprotein B in vitro in cell‐free lysates of HepG2 cells: evidence that insulin modulates ApoB synthesis at the translational level. Clin. Biochem. 25: 321–323, 1997.
 388. Theriault, A., G. Ogbonna, and K. Adeli. Thyroid hormone modulates apolipoprotein B gene expression in HepG2 cells. Biochem. Biophys. Res. Commun. 186: 617–623, 1992.
 389. Uchida, E., A. Masumoto, S. Sakamoto, S. Koga, and H. Nawata. Effect of insulin, glucagon or dexamethasone on the production of apolipoprotein A‐IV in cultured rat hepatocytes. Atherosclerosis 87: 195–202, 1991.
 390. Uusitupa, M., O. Siitonen, E. Voutilainen, A. Aro, K. Hersio, K. Pyorala, I. Penttila, and C. Ehnholm. Serum lipids and lipoproteins in newly diagnosed non‐insulin‐dependent (type II) diabetic patients with special reference to factors influencing HDL‐cholesterol and triglyceride levels. Diabetes Care 9: 17–22, 1986.
 391. Van Golde, L. M. G., B. Fleischer, and S. Fleischer. Some studies on the metabolism of phospholipids in Golgi complex from bovine and rat liver in comparison to other subcellular fractions. Biochim. Biophys. Acta 249: 318–330, 1971.
 392. Vance, J. E.. The use of newly synthesized phospholipids for assembly into secreted hepatic lipoproteins. Biochim. Biophys. Acta 1006: 59–69, 1989.
 393. Vance, J. E., and D. E. Vance. Lipoprotein assembly and secretion by hepatocytes. Annu. Rev. Nutr. 10: 337–356, 1990.
 394. Vega, G. L., R. M. Krauss, and S. M. Grundy. Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B‐containing lipoproteins. J. Intern. Med. 227: 81–94, 1990.
 395. Wallinder, L., J. Peterson, T. Olivecrona, and G. Bengtsson‐Olivecrona. Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase. Biochim. Biophys. Acta 769: 513–524, 1984.
 396. Walsh, B. W., and F. M. Sacks. Effects of low dose oral contraceptives on very low density and low density lipoprotein metabolism. J. Clin. Invest. 91: 2126–2132, 1993.
 397. Weight, M. J., H. S. Coetzee, C. M. Smuts, M. P. Marais, J. S. Maritz, F. S. Hough, A. J. Benade, and J. J. Taljaard. Lecithin: cholesterol acyltransferase activity and high‐density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control. Acta Diabetol 30: 159–165, 1993.
 398. Weisgraber, K. H., R. W. Mahley, R. C. Kowal, J. L. Goldstein, and M. S. Brown. Apolipoprotein C‐I modulates the interaction of apolipoprotein E with beta‐migrating very low density lipoproteins (beta‐VLDL) and inhibits binding of beta‐VLDL to low density lipoprotein receptor‐related protein. J. Biol. Chem. 265: 22453–22459, 1990.
 399. Weisweiler, P., M. Drosner, and P. Schwandt. Dietary effects on very low density lipoprotein in type 2 (non‐insulin dependent) diabetes mellitus. Diabetologia 23: 101–104, 1982.
 400. Wentworth, M. A., T. O'Brien, A. Rastogi, and B. A. Kottke. Apolipoprotein A‐II levels and coronary artery disease in subjects with and without diabetes: a study with use of a specific radioimmunoassay for apolipoprotein A‐II. Mayo Clin. Proc. 68: 556–560, 1993.
 401. Wetterau, J. R., L. P. Aggerbeck, M. E. Bouma, C. Eisenberg, A. Munck, M. Hermier, J. Schmitz, G. Gay, D. J. Rader, and R. E. Gregg. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 258: 999–1001, 1992.
 402. Wetterau, J. R., K. A. Combs, S. N. Spinner, and B. J. Joiner. Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex. J. Biol. Chem. 265: 9800–9807, 1990.
 403. Wetterau, J. R., and D. B. Zilversmith. Localization of intracellular triglyceride and cholesterol ester transfer activity. Biochim. Biophys. Acta 875: 610–617, 1986.
 404. Wilkinson, J., J. A. Higgins, P. Groot, E. Gherardi, and D. Bowyer. Topography of apolipoprotein B in subcellular fractions of rabbit liver probed with a panel of monoclonal antibodies. J. Lipid Res. 34: 815–825, 1993.
 405. Williams, K. J., G. M. Fless, K. A. Petrie, M. L. Snyder, R. W. Brocia, and T. L. Swenson. Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. J. Biol. Chem. 19: 13284–13292, 1992.
 406. Willnow, T. E., Z. Sheng, S. Ishibashi, and J. Herz. Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist. Science 264: 1471–1474, 1994.
 407. Windler, E., Y. Chao, and R. J. Havel. Determinants of hepatic uptake of triglyceride‐rich lipoproteins and their remnants in the rat. J. Biol. Chem. 255: 5475–5480, 1980.
 408. Windler, E., Y. Chao, and R. J. Havel. Regulation of the hepatic uptake of triglyceride‐rich lipoproteins in the rat: opposing effects of homologous apolipoprotein E and individual C apoproteins. J. Biol. Chem. 255: 8303–8307, 1980.
 409. Winocour, P. H., P. N. Durrington, M. Ishola, and D. C. Anderson. Lipoprotein abnormalities in insulin‐dependent diabetes mellitus. Lancet 1: 1176–1179, 1986.
 410. Witztum, J. L., E. M. Mahoney, and M. J. Branks. Nonenzymatic glucosylation of low‐density lipoprotein alters its biologic activity. Diabetes 31: 283–291, 1982.
 411. Witztum, J. L., M. Fisher, T. Pietro, U. P. Steinbrecher, and R. L. Elam. Nonenzymatic glucosylation of high‐density lipoprotein accelerates its catabolism in guinea pigs. Diabetes 31: 1029–1032, 1982.
 412. Wu, X., N. Sakata, J. L. Dixon, and H. N. Ginsberg. Exogenous VLDL stimulates apolipoprotein from HepG2 cells by both preand post‐translantional mechanisms. J. Lipid Res. 35: 1200–1210, 1994.
 413. Wu, X., N. Sakata, E. Lui, and H. N. Ginsberg. Evidence for a lack of regulation of the assembly and secretion of apolipoprotein B‐containing lipoprotein from HepG2 cells by cholesteryl ester. J. Biol. Chem. 269: 12375–12382, 1994.
 414. Wu, X., M. Zhou, L. Huang, J. Wetterau, and H. N. Ginsberg. Demonstration of a physical interaction between microsomal triglyceride transfer protein and apolipoprotein B during the assembly of apo B‐containing lipoproteins. J. Biol. Chem. 271: 10277–10281, 1996.
 415. Yamada, N., D. M. Shames, J. B. Stoudemire, and R. J. Havel. Metabolism of lipoproteins containing apolipoprotein B‐100 in blood plasma of rabbits: heterogeneity related to the presence of apolipoprotein E. Proc. Natl. Acad. Sci. U.S.A. 83: 3479–3483, 1986.
 416. Yamamoto, K., H. Shimano, M. Shimada, M. Kawamura, T. Gotoda, K. Harada, J. Ohsuga, Y. Yazaki, and N. Yamada. Overexpression of apolipoprotein E prevents development of diabetic hyperlipidemia in transgenic mice. Diabetes 44: 580–585, 1995.
 417. Yamane, M., S. Jiao, S. Kihara, I. Shimomura, K. Yanagi, and K. Tokunaga. Increased proportion of plasma apoB‐48 to apoB‐100 in non‐insulin‐dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver. J. Lipid Res. 36: 1676–1685, 1995.
 418. Yang, C., S. Chen, S. H. Gianturco, W. A. Bradley, J. T. Sparrow, M. Tanimura, W. Li, D. A. Sparrow, H. De Loof, M. Rosseneu, F. Lee, Z. Gu, J. Gotto, and L. Chan. Sequence, structure, receptor‐binding domains and internal repeats of human apolipoprotein B‐100. Nature 323: 738–742, 1986.
 419. Yang, C., Z. Gu, S. Weng, T. W. Kim, S. Chen, H. J. Pownall, P. M. Sharp, S. Liu, W. Li, A. M. Gotto, Jr., and L. Chan. Structure of apolipoprotein B‐100 of human low density lipoproteins. Arteriosclerosis 9: 96–108, 1989.
 420. Yeaman, S. J., G. M. Smith, C. A. Jepson, S. L. Wood, and N. Emmison. The multifunctional role of hormone‐sensitive lipase in lipid metabolism. Adv. Enzyme Regul. 34: 355–370, 1994.
 421. Yeung, S. J., S. H. Chen, and L. Chan. Ubiquitin‐proteasome pathway mediates intracellular degradation of apolipoprotein B. Biochemistry 35: 13843–13848, 1996.
 422. Yki‐Jarvinen, H., and M. Taskinen. Interrelationship among insulin's antilipolytic and glucoregulatory effects and plasma triglycerides in nondiabetic and diabetic patients with endogenous hypertriglyceridemia. Diabetes 37: 1271–1278, 1988.
 423. Yoshino, G., T. Kazumi, M. Iwai, K. Matsuba, I. Iwatani, M. Matsushita, T. Kasama, and S. Baba. Recommendation for strict control of plasma triglyceYide in diabetic subjects. Diabetes Care 11: 794–795, 1988.
 424. Yost, T. J., K. K. Froyd, D. R. Jensen, and R. H. Eckel. Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non‐insulin‐dependent diabetes mellitus. Metabolism 44: 786–790, 1995.
 425. Young, S. G.. Recent progress in understanding apolipoprotein B. Circulation 82: 1574–1594, 1990.
 426. Zannis, V. I.. Molecular biology of human apolipoproteins B and E and associated diseases of lipoprotein metabolism. Adv. Lipid Res. 23: 1–64, 1989.
 427. Zhang, S. H., R. L. Reddick, J. A. Piedrahita, and N. Maeda. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258: 468, 1992.
 428. Zhong, S., I. J. Goldberg, C. Bruce, E. Rubin, J. L. Breslow, and A. Tall. Human ApoA‐II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice. J. Clin. Invest. 94: 2457–2467, 1994.
 429. Zhou, M., X. Wu, L. Huang, and H. Ginsberg. Apolipoprotein B100, an inefficiently translocated secretory protein, is bound to a cytosolic chaperone, heat shock protein 70. J. Biol. Chem. 270: 25220–25224, 1995.

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Article Title: The Pancreas and Lipoprotein Metabolism
 

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Henry N. Ginsberg, Ira J. Goldberg. The Pancreas and Lipoprotein Metabolism. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 675-706. First published in print 2001. doi: 10.1002/cphy.cp070222