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Regulation of Glycogen Metabolism

Peter J. Roach, Alexander V. Skurat, Robert A. Harris

10.1002/cphy.cp070219

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 Glycogen
1.1 Structure
1.2 Function
2 Pathways of Glycogen Metabolism
2.1 Overview
2.2 Glycogen Biosynthesis
2.3 Glycogen Synthase and Branching Enzyme
2.4 Glycogenolysis and Debranching Enzyme
2.5 Glycogen Particles and Physical Interactions among Glycogen‐Metabolizing Proteins
3 Hormonal Regulation of Glycogen Synthesis in Muscle
3.1 Insulin
3.2 Mechanisms of Insulin Action
3.3 Epinephrine
4 Regulation of Glycogen Metabolism in Liver
4.1 Overview
4.2 Two Pathways of Glycogen Synthesis in Liver
4.3 Glucose Transport Is Not Regulated in Liver
4.4 Regulation of Glucokinase Activity
4.5 Regulation of Glycogen Synthase Activity
4.6 Regulation of Glucose‐6‐Phosphatase Activity
4.7 Regulation of Glycogen Phosphorylase Activity
5 Conclusion
Figure 1. Figure 1.

Predominant glycosidic linkages in glycogen.
Figure 2. Figure 2.

Model for branched structure of glycogen. Heavy lines indicate oligosaccharide chains and light lines, different tiers of glycogen structure. Chains are either unbranched (A) or branched (B). Filled circle indicates glycogenin attached to reducing end. Based on model of Melendez‐Hevia, et al. 224.
Figure 3. Figure 3.

Relevant metabolic pathways of muscle and liver. Metabolites: Glc, glucose; G6P, glucose‐6‐phosphate; G1P, glucose‐1‐phosphate; F6P, fructose‐6‐phosphate UDP‐Glc, UDP‐glucose; F1,6P2, fructose‐1,6‐bisphosphate. Enzymes: GLUT, glucose transporter; HK, hexokinase; G6Pase, glucose‐6‐phosphatase; PFK1, 6‐phosphofructo‐1‐kinase; F1,6P2ase, fructose‐1,6‐bisphosphatase; GP, glycogen phosphorylase; GS, glycogen synthase.
Figure 4. Figure 4.

Pathway of glycogen biosynthesis. GN, glycogenin; Glc, glucose.
Figure 5. Figure 5.

Glycogen synthase phosphorylation. Nine sites of phosphorylation (P) in rabbit muscle glycogen synthase are shown together with several protein kinases which phosphorylate these sites in vitro. CaM‐PK, calmodulin‐dependent protein kinase II; cGMP‐PK, GMP‐dependent protein kinase; CK‐I, casein kinase 1; CK‐II, casein kinase II; GSK‐3, glycogen synthase kinase‐3; MAPKAP, Kinase‐2 mitogen‐activated protein kinase‐actuated protein kinase‐2
Figure 6. Figure 6.

Alternate models of glycogen synthase COOH‐terminal phosphorylation. A: The original hierarchal phosphorylation model proposed by Fiol et al. 95. B: The possibility of alternate mechanisms for modifying sites 3a and 3b, the two COOH‐terminal sites with greatest effect on enzyme activity. GSK‐3, glycogen synthase kinase‐3; CK, casein kinase; PK, protein kinase.
Figure 7. Figure 7.

Insulin signaling. Current models for the control of glycogen synthase (GS) by insulin are depicted. Subscript P indicates covalent phosphorylation. Arrows indicate activating inputs and bars, inhibitory ones. Dashed lines indicate pathways that are less certain than solid lines. IRS, insulin receptor substrate; PI, phosphatidylinositol, PDK, phosphoinositide‐dependent kinase; PKB, protein kinase B; GSK‐3, glycogen synthase kinase‐3; PP1G, glycogen‐associated protein phosphatase; GP, glycogen phosphorylase.
Figure 8. Figure 8.

Epinephrine and glucagon signaling. β‐AR, β‐adrenergc receptor; GR, glucagon receptor; cAMPPK, AMP‐dependent protein kinase; PhK, phosphorylase kinase; GS, glycogen synthase; GP, glycogen phosphorylase; PP1G, glycogen‐associated protein phosphatase, of which there may be several forms (see text); subscript P, covalent phosphorylation.
Figure 9. Figure 9.

Liver glycogen biosynthesis. Glc, glucose; G6P, glucose‐6‐phosphate; GIP, glucose‐1‐phosphate; UDP‐Glc, UDP‐glucose; F1,6P2, fructose‐1,6‐bisphosphate; PP1‐GL, glycogen‐assoeiated protein phosphatase (liver); subscript P, covalent phosphorylation. Enzymes: GLUT‐2, glucose transporter; GK, glucokinase; GK‐RP, glucokinase regulatory protein complex; GP, glycogen phosphorylase; GS, glycogen synthase. Bold arrows indicate physical translocations proposed to occur upon stimulation of glycogen synthesis by elevated glucose levels in the blood. Box defined by dashed lines corresponds to the hypothetical site of glycogen synthesis. Translocation of glycogen synthase does not necessarily require that the enzyme first be dephosphorylated.


Figure 1.

Predominant glycosidic linkages in glycogen.



Figure 2.

Model for branched structure of glycogen. Heavy lines indicate oligosaccharide chains and light lines, different tiers of glycogen structure. Chains are either unbranched (A) or branched (B). Filled circle indicates glycogenin attached to reducing end. Based on model of Melendez‐Hevia, et al. 224.



Figure 3.

Relevant metabolic pathways of muscle and liver. Metabolites: Glc, glucose; G6P, glucose‐6‐phosphate; G1P, glucose‐1‐phosphate; F6P, fructose‐6‐phosphate UDP‐Glc, UDP‐glucose; F1,6P2, fructose‐1,6‐bisphosphate. Enzymes: GLUT, glucose transporter; HK, hexokinase; G6Pase, glucose‐6‐phosphatase; PFK1, 6‐phosphofructo‐1‐kinase; F1,6P2ase, fructose‐1,6‐bisphosphatase; GP, glycogen phosphorylase; GS, glycogen synthase.



Figure 4.

Pathway of glycogen biosynthesis. GN, glycogenin; Glc, glucose.



Figure 5.

Glycogen synthase phosphorylation. Nine sites of phosphorylation (P) in rabbit muscle glycogen synthase are shown together with several protein kinases which phosphorylate these sites in vitro. CaM‐PK, calmodulin‐dependent protein kinase II; cGMP‐PK, GMP‐dependent protein kinase; CK‐I, casein kinase 1; CK‐II, casein kinase II; GSK‐3, glycogen synthase kinase‐3; MAPKAP, Kinase‐2 mitogen‐activated protein kinase‐actuated protein kinase‐2



Figure 6.

Alternate models of glycogen synthase COOH‐terminal phosphorylation. A: The original hierarchal phosphorylation model proposed by Fiol et al. 95. B: The possibility of alternate mechanisms for modifying sites 3a and 3b, the two COOH‐terminal sites with greatest effect on enzyme activity. GSK‐3, glycogen synthase kinase‐3; CK, casein kinase; PK, protein kinase.



Figure 7.

Insulin signaling. Current models for the control of glycogen synthase (GS) by insulin are depicted. Subscript P indicates covalent phosphorylation. Arrows indicate activating inputs and bars, inhibitory ones. Dashed lines indicate pathways that are less certain than solid lines. IRS, insulin receptor substrate; PI, phosphatidylinositol, PDK, phosphoinositide‐dependent kinase; PKB, protein kinase B; GSK‐3, glycogen synthase kinase‐3; PP1G, glycogen‐associated protein phosphatase; GP, glycogen phosphorylase.



Figure 8.

Epinephrine and glucagon signaling. β‐AR, β‐adrenergc receptor; GR, glucagon receptor; cAMPPK, AMP‐dependent protein kinase; PhK, phosphorylase kinase; GS, glycogen synthase; GP, glycogen phosphorylase; PP1G, glycogen‐associated protein phosphatase, of which there may be several forms (see text); subscript P, covalent phosphorylation.



Figure 9.

Liver glycogen biosynthesis. Glc, glucose; G6P, glucose‐6‐phosphate; GIP, glucose‐1‐phosphate; UDP‐Glc, UDP‐glucose; F1,6P2, fructose‐1,6‐bisphosphate; PP1‐GL, glycogen‐assoeiated protein phosphatase (liver); subscript P, covalent phosphorylation. Enzymes: GLUT‐2, glucose transporter; GK, glucokinase; GK‐RP, glucokinase regulatory protein complex; GP, glycogen phosphorylase; GS, glycogen synthase. Bold arrows indicate physical translocations proposed to occur upon stimulation of glycogen synthesis by elevated glucose levels in the blood. Box defined by dashed lines corresponds to the hypothetical site of glycogen synthesis. Translocation of glycogen synthase does not necessarily require that the enzyme first be dephosphorylated.

References
 1. Agius, L., and M. Peak. Binding and translocation of glucokinase in hepatocytes. Biochem. Soc. Trans. 25: 145–1450, 1997.
 2. Agius, L., and M. Peak. Intracellular binding of glucokinase in hepatocytes and translocation by glucose, fructose and insulin. Biochem. J. 296: 785–796, 1993.
 3. Agius, L., M. Peak, C. B. Newgard, A. M. Gomez‐Foix, and J. J. Guinovart. Evidence for a role of glucose‐induced translocation of glucokinase in the control of hepatic glycogen synthesis. J. Biol. Chem. 271: 30479–30486, 1996.
 4. Agius, L., M. Peak, and E. Van Schaftingen. The regulatory protein of glucokinase binds to the hepatocyte matrix, but, unlike glucokinase, does not translocate during substrate stimulation. Biochem. J. 309: 711–713, 1995.
 5. Aledo, J. C., L. Lavoie, A. Volchuk, S. R. Keller, A. Klip, and H. S. Hundal. Identification and characterization of two distinct intracellular GLUT4 pools in rat skeletal muscle: evidence for an endosomal and an insulin‐sensitive GLUT4 compartment. Biochem. J. 325: 727–732, 1997.
 6. Alemany, S., and P. Cohen. Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase‐1. FEBS Lett. 198: 194–202, 1986.
 7. Alessi, D. R., M. Andjelkovic, B. Caudwell, P. Cron, N. Morrice, P. Cohen, and B. A. Hemmings. Mechanism of activation of protein kinase B by insulin and IGF‐1. EMBO J. 15: 6541–6551, 1996.
 8. Alessi, D. R., S. R. James, C. P. Downes, A. B. Holmes, P. R. Gaffney, C. B. Reese, and P. Cohen. Characterization of a 3‐phosphoinositide‐dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr. Biol. 7: 261–269, 1997.
 9. Alonso, M. D., J. Lomako, W. M. Lomako, and W. J. Whelan. A new look at the biogenesis of glycogen. FASEB J. 9: 1126–1137, 1995.
 10. Alonso, M. D., J. Lomako, W. M. Lomako, and W. J. Whelan. Tyrosine‐194 of glycogenin undergoes autocatalytic glucosylation but is not essential for catalytic function and activity. FEBS Lett. 342: 38–12, 1994.
 11. Alonso, M. D., J. Lomako, W. M. Lomako, W.J. Whelan, and J. Preiss. Properties of carbohydrate‐free recombinant glycogenin expressed in an Escherichia coli mutant lacking UDP‐glucose pyrophosphorylase activity. FEBS Lett. 352: 222–226, 1994.
 12. Andjelkovic, M., T. Jakubowicz, P. Cron, X. F. Ming, J. W. Han, and B. A. Hemmings. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC‐PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc. Natl. Acad. Sci. U.S.A. 93: 5699–5704, 1996.
 13. Appleman, M. M., E. G. Krebs, and E. H. Fischer. Purification and properties of inactive liver phosphorylase. Biochemistry 5: 2101–2107, 1996.
 14. Araki, E., M. A. Lipes, M. E. Patti, J. C. Bruning, B. R. Haag, R. S. Johnson, and C. R. Kahn. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS‐1 gene [see comments]. Nature 372: 186–190, 1994.
 15. Argaud, D., T. L. Kirby, C. B. Newgard, and A. J. Lange. Stimulation of glucose‐6‐phosphatase gene expression by glucose and fructose‐2, 6‐bisphosphate. J. Biol. Chem. 272: 12854–12861, 1997.
 16. Armstrong, C. G., G. J. Browne, P. Cohen, and P. T. Cohen. PPP1R6, a novel member of the family of glycogen‐targetting subunits of protein phosphatase 1. FEBS Lett. 418: 210–214, 1997.
 17. Azpiazu, I., A. R. Saltiel, A. A. De Paoli‐Roach, and J. C. Lawrence. Regulation of both glycogen synthase and PHAS‐1 by insulin in rat skeletal muscle involves mitogen‐activated protein kinase‐independent and rapamycin‐sensitive pathways. J. Biol. Chem. 271: 5033–5039, 1996.
 18. Babu, Y. S., C. E. Bugg, and W. J. Cook. Structure of calmodulin refined at 2.2 Å resolution. J. Mol. Biol. 204: 191–204, 1988.
 19. Backer, J. M., M. G. Myers, Jr., X. J. Sun, D. J. Chin, S. E. Shoelson, M. Miralpeix, and M. F. White. Association of IRS‐1 with the insulin receptor and the phosphatidylinositol 3′‐kinase. Formation of binary and ternary signaling complexes in intact cells. J. Biol. Chem. 268: 8204–8212, 1993.
 20. Bai, G., Z. J. Zhang, R. Werner, F. Q. Nuttall, A. W. Tan, and E. Y. Lee. The primary structure of rat liver glycogen synthase deduced by cDNA cloning. Absence of phosphorylation sites la and lb. J. Biol. Chem. 265: 7843–7848, 1990.
 21. Bailey, J. M., J. P. Lomako, W. Lomkako, and W. J. Whelan. The role of glycogenin in glycogen synthesis and non‐insulin dependent diabetes mellitus. Biochem. Soc. Trans. 21: 124S, 1993.
 22. Bali, D., A. Svetlanov, H. W. Lee, et al. Animal model for maturityonset diabetes of the young generated by disruption of the mouse glucokinase gene. J. Biol. Chem. 270: 21464–21467, 1995.
 23. Ball, S., H. P. Guan, M. James, A. Myers, P. Keeling, G. Mouille. A. Buleon, P. Colonna, and J. Preiss. From glycogen to amylopectin: a model for the biogenesis of the plant starch granule. Cell 86: 349–352, 1996.
 24. Bao, Y., T. L. Dawson, Jr., and Y. T. Chen. Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5′ flanking region. Genomics 38: 155–165, 1996.
 25. Bao, Y., P. Kishnani, J. Y. Wu, and Y. T. Chen. Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen‐branching enzyme gene. J. Clin. Invest. 97: 941–948, 1996.
 26. Baque, S., J. J. Guinovart, and J. C. Ferrer. Glycogenin, the primer of glycogen synthesis, binds to actin. FEBS Lett. 417: 355–359, 1997.
 27. Barber, A. A., S. A. J. Orrell, and E. Bueding. Association of enzymes with rat liver glycogen isolated by rate‐zonal centrifugation. J. Biol. Chem. 242: 4040–4044, 1967.
 28. Barzilai, N., and L. Rossetti. Role of glucokinase and glucose‐6‐phosphatase in the acute and chronic regulation of hepatic glucose fluxes by insulin. J. Biol Chem. 268: 25019–25025, 1993.
 29. Bates, E. J., G. M. Heaton, C. Taylor, J. C. Kernohan, and P. Cohen. Debranching enzyme from rabbit skeletal muscle; evidence for the location of two active centres on a single polypeptide chain. FEBS Lett. 58: 181–185, 1975.
 30. Bellacosa, A., J. R. Testa, S. P. Staal, and P. N. Tsichlis. A retroviral oncogene, akt, encoding a serine‐threonine kinase containing an SH2‐like region. Science 254: 274–277, 1991.
 31. Birnbaum, M. J.. The insulin‐sensitive glucose transporter. Int. Rev. Cytol. 137: 239–297, 1992.
 32. Bollen, M., and W. Stalmans. The structure, role, and regulation of type 1 protein phosphatases. Crit. Rev. Biochem. Mol. Biol. 27: 227–281, 1992.
 33. Borthwick, A. C., A.M. Wells, J. J. Rochford, S. J. Hurel, D. M. Turnbull, and S. J. Yeaman. Inhibition of glycogen synthase kinase‐3 by insulin in cultured human skeletal muscle myoblasts. Biochem. Biophys. Res. Commun. 210: 738–745, 1995.
 34. Bossard, P., J. F. Decaux, M. Juanes, and J. Girard. Initial expression of glucokinase gene in cultured hepatocytes from suckling rats is linked to the synthesis of an insulin‐dependent protein. Eur. J. Biochem. 223: 371–380, 1994.
 35. Brady, M. J., J. A. Printen, C. C. Mastick, and A. R. Saltiel. Role of protein targeting to glycogen (PTG) in the regulation of protein phosphatase‐1 activity. J. Biol. Chem. 272: 20198–20204, 1997.
 36. Brown, D. H., and B. Illingworth. Proc. Natl. Acad. Sci. U.S.A. 48: 1783–1787, 1962.
 37. Brown, K. S., S. S. Kalinowski, J. R. Megill, S. K. Durham, and K. A. Mookhtiar. Glucokinase regulatory protein may interact with glucokinase in the hepatocyte nucleus. Diabetes 46: 179–186, 1997.
 38. Browner, M. F., K. Nakano, A. G. Bang, and R. J. Fletterick. Human muscle glycogen synthase cDNA sequence: a negatively charged protein with an asymmetric charge distribution. Proc. Natl. Acad. Sci. U.S.A. 86: 1443–1447, 1989.
 39. Brunn, G. J., J. Williams, C. Sabers, G. Wiederrecht, J. C. Lawrence, Jr., and R. T. Abraham. Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3–kinase inhibitors, wortmannin and LY294002. EMBO J. 15: 5256–5267, 1996.
 40. Burgering, B. M., and P. J. Coffer. Protein kinase B (c‐Akt) in phosphatidylinositol‐3‐OH kinase signal transduction [see comments]. Nature 376: 599–602, 1995.
 41. Cadefau, J., M. Bollen, and W. Stalmans. Glucose‐induced glycogenosis in the liver involves the glucose‐6‐phosphate‐dependent dephosphorylation of glycogen synthase. Biochem. J. 322: 745–750, 1997.
 42. Camici, M., Z. Ahmad, A. A. De Paoli‐Roach, and P. J. Roach. Phosphorylation of rabbit liver glycogen synthase by multiple protein kinases. J. Biol Chem. 259: 2466–2473, 1984.
 43. Camici, M., A. A. De Paoli‐Roach, and P. J. Roach. Rabbit liver glycogen synthase. Purification and comparison of the properties of glucose‐6‐P‐dependent and glucose‐6‐P‐independent forms of the enzyme. J. Biol. Chem. 259: 3429–3434, 1984.
 44. Campbell, D. G., and P. Cohen. The amino acid sequence of rabbit skeletal muscle glycogenin. Eur. J. Biochem. 185: 119–125, 1989.
 45. Cannon, J. F., J. R. Pringle, A. Fiechter, and M. Khalil. Characterization of glycogen‐deficient glc mutants of Saccharomyces cerevisiae. Genetics 136: 485–503, 1994.
 46. Cao, Y., A. M. Mahrenholz, A. A. De Paoli‐Roach, and P. J. Roach. Characterization of rabbit skeletal muscle glycogenin. Tyrosine 194 is essential for function. J. Biol. Chem. 268: 14687–14693, 1993.
 47. Cao, Y., A. V. Skurat, A. A. De Paoli‐Roach, and P. J. Roach. Initiation of glycogen synthesis. Control of glycogenin by glycogen phosphorylase. J. Biol. Chem. 268: 21717–21721, 1993.
 48. Cao, Y., L. K. Steinrauf, and P. J. Roach. Mechanism of glycogenin self‐glucosylation. Arch. Biochem. Biophys. 319: 293–298, 1995.
 49. Carabaza, A., C. J. Ciudad, S. Baque, and J. J. Guinovart. Glucose has to be phosphorylated to activate glycogen synthase, but not to inactivate glycogen phosphorylase in hepatocytes. FEBS Lett. 296: 211–214, 1992.
 50. Carling, D., and D. G. Hardie. The substrate and sequence specificity of the AMP‐activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochim. Biophys. Acta 1012: 81–86, 1989.
 51. Caudwell, F. B., and P. Cohen. Purification and subunit structure of glycogen‐branching enzyme from rabbit skeletal muscle. Eur. J. Biochem. 109: 391–394, 1980.
 52. Challiss, R. A., B. Crabtree, and E. A. Newsholme. Hormonal regulation of the rate of the glycogen/glucose‐1‐phosphate cycle in skeletal muscle. Eur. J. Biochem. 163: 205–210, 1987.
 53. Cheatham, B., C. J. Vlahos, L. Cheatham, L. Wang, J. Blenis, and C. R. Kahn. Phosphatidylinositol 3‐kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14: 4902–4911, 1994.
 54. Cheng, A., T. J. Fitzgerald, and G. M. Carlson. Adenosine 5′‐diphosphate as an allosteric effector of phosphorylase kinase from rabbit skeletal muscle. J. Biol. Chem. 260: 2535–2542, 1985.
 55. Cheng, C., D. Huang, and P. J. Roach. Yeast PIG genes: PIG1 encodes a putative type 1 phosphatase subunit that interacts with the yeast glycogen synthase Gsy2p. Yeast 13: 1–8, 1997.
 56. Cheng, C., J. Mu, I. Farkas, D. Huang, M. G. Goebl, and P. J. Roach. Requirement of the self‐glucosylating initiator proteins Glg1p and Glg2p for glycogen accumulation in Saccharomyces cerevisiae. Mol Cell. Biol. 15: 6632–6640, 1995.
 57. Ciudad, C. J., F. Bosch, and J. J. Guinovart. Insulin activation of basal hepatic glycogen synthase. FEBS Lett. 129: 123–126, 1981.
 58. Ciudad, C. J., A. Carabaza, F. Bosch, I. F. A. M. Gomez, and J. J. Guinovart. Glycogen synthase activation by sugars in isolated hepatocytes. Arch. Biochem. Biophys. 264: 30–39, 1988.
 59. Ciudad, C. J., J. Massague, and J. J. Guinovart. The inactivation of glycogen phosphorylase is not a prerequisite for the activation of liver glycogen synthase. FEBS Lett. 99: 321–324, 1979.
 60. Clarke, J. F., P. W. Young, K. Yonezawa, M. Kasuga, and G. D. Holman. Inhibition of the translocation of GLUT1 and GLUT4 in 3T3‐L1 cells by the phosphatidylinositol 3‐kinase inhibitor, wortmannin. Biochem. J. 300: 631–635, 1994.
 61. Coffer, P. J., and J. R. Woodgett. Molecular cloning and characterisation of a novel putative protein‐serine kinase related to the cAMP‐dependent and protein kinase C families Eur. J. Biochem. 201: 475–481, 1991.
 62. Cohen, P.. Muscle glycogen synthase. In: The Enzymes (3rd ed.), edited by P. D. Boyer and E. G. Krebs. Orlando, FL: Academic, 1986. vol. 17A, p. 461–497.
 63. Cohen, P.. The hormonal control of glycogen metabolism in mammalian muscle by multivalent phosphorylation. Biochem. Soc. Trans. 7: 459–80, 1979.
 64. Cohen, P.. The role of phosphorylase kinase in the nerves and hormonal, control of glycogenolysis in muscle. Biochem. Soc. Symp. 39: 51–73, 1974.
 65. Cohen, P., and P. T. Cohen. Protein phosphatases come of age. J. Biol. Chem. 264: 21435–21438, 1989.
 66. Cohen, P., and D. G. Hardie. The actions of cyclic AMP on biosynthetic processes are mediated indirectly by cyclic AMP‐dependent protein kinase. Biochim. Biophys. Acta 1094: 292–299, 1991.
 67. Cong, L.‐N., H. Chen, Y. Li, L. Zhou, M. A. McGibbon, S. I. Taylor, and M. J. Quon. Physiological role of Act in insulin‐stimulated translocation of GLUT4 in transfected rat adipose cells. Mol. Endocrinol. 11: 1881–1890, 1997.
 68. Craik, J. D., and K. R. Elliott. Kinetics of 3–O‐methyl‐D‐glucose transport in isolated rat hepatocytes. Biochem. J. 182: 503–508, 1979.
 69. Cross, D. A., D. R. Alessi, P. Cohen, M. Andjelkovich, and B. A. Hemmings. Inhibition of glycogen synthase kinase‐3 by insulin mediated by protein kinase B. Nature 378: 785–789, 1995.
 70. Dasgupta, M., T. Honeycutt, and D. K. Blumenthal. The gammasubunit of skeletal muscle phosphorylase kinase contains two non‐contiguous domains that act in concert to bind calmodulin. J. Biol. Chem. 264: 17156–17163, 1989.
 71. Davidson, J. J., T. Ozcelik, C. Hamacher, P. J. Willems, U. Francke, and M. W. Kilimann. cDNA cloning of a liver isoform of the phosphorylase kinase alpha subunit and mapping of the gene to Xp22.2‐p22.1, the region of human X‐linked liver glycogenosis. Proc. Natl Acad. Sci. U.S.A. 89: 2096–2100, 1992.
 72. Dent, P., D. G. Campbell, F. B. Caudwell, and P. Cohen. Identification of three in vivo phosphorylation sites on the glycogenbinding subunit of protein phosphatase 1 from rabbit skeletal muscle, and their response to adrenaline. FEBS Lett. 259: 281–285, 1990.
 73. Dent, P., A. Lavoinne, S. Nakielny, F. B. Caudwell, P. Watt, and P. Cohen. The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle [see comments]. Nature 348: 302–308, 1990.
 74. Depaoli‐Roach, A. A., I. K. Park, V. Cerovsky, C. Csortos, S. D. Durbin, M. J. Kuntz, A. Sitikov, P. M. Tang, A. Verin, and S. Zolnierowicz. Serine/threonine protein phosphatases in the control of cell function. Adv. Enzyme Regul. 34: 199–224, 1994.
 75. Doherty, M. J., G. Moorhead, N. Morrice, P. Cohen, and P. T. Cohen. Amino acid sequence and expression of the hepatic glycogen‐binding (GL)‐subunit of protein phosphatase‐1. FEBS Lett. 375: 294–298, 1995.
 76. Doherty, M. J., P. R. Young, and P. T. Cohen. Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which is related to the liver‐ and muscle‐specific glycogen binding subunits of protein phosphatase 1. FEBS Lett. 399: 339–343, 1996.
 77. Drochmans, P.. Morphologie du glycogene. Etude du miscroscope electronique de colorations negative du glycogene particulaire. J. Ultrastruct. Res. 6: 141–163, 1962.
 78. Dworkin, M. B., and E. Dworkin‐Rastl. Carbon metabolism in early amphibian embryos. Trends Biochem. Sci. 16: 229–234, 1991.
 79. Eichner, R. D.. Adipose tissue glycogen synthesis. Int. J. Biochem. 16: 257–261, 1984.
 80. Eldar‐Finkelman, H., G. M. Argast, O. Foord, E. H. Fischer, and E. G. Krebs. Expression and characterization of glycogen synthase kinase‐3 mutants and their effect on glycogen synthase activity in intact cells. Proc. Natl. Acad. Sci. U.S.A. 93: 10228–10233, 1996.
 81. Embi, N., P. J. Parker, and P. Cohen. A reinvestigation of the phosphorylation of rabbit skeletal‐muscle glycogen synthase by cyclic‐AMP‐dependent protein kinase. Identification of the third site of phosphorylation as serine‐7. Eur. J. Biochem. 115: 405–413, 1981.
 82. Embi, N., D. B. Rylatt, and P. Cohen. Glycogen synthase kinase‐3 from rabbit skeletal muscle. Separation from cyclic‐AMP‐dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 107: 519–527, 1980.
 83. Ercan, N., M. C. Gannon, and F. Q. Nuttall. Incorporation of glycogenin into a hepatic proteoglycogen after oral glucose administration. J. Biol. Chem. 269: 22328–22333, 1994.
 84. Espinoza, F. H., J. Ogas, I. Herskowitz, and D. O. Morgan. Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase PHO85. Science 266: 1388–1391, 1994.
 85. Farkas, I., T. A. Hardy, M. G. Goebl, and P. J. Roach. Two Saccharomyces cerevisiae are coded by distinct genes that are differentially controlled. J. Biol. Chem. 266: 15602–15607, 1991.
 86. Farkas, I., B. Toth, G. Bot, and P. Gergely. Hormonal regulation of phosphorylase phosphatase activity in rat liver. FEBS Lett. 203: 253–256, 1986.
 87. Feng, Z. H., S. E. Wilson, Z. Y. Peng, K. K. Schlender, E. M. Reimann, and R. J. Trumbly. The yeast GLC7 gene required for glycogen accumulation encodes a type 1 protein phosphatase. J. Biol. Chem. 266: 23796–23801, 1991.
 88. Fernandez‐Novell, J. M., J. Arino, and J. J. Guinovart. Effects of glucose on the activation and translocation of glycogen synthase in diabetic rat hepatocytes. Eur. J. Biochem. 226: 665–671, 1994.
 89. Fernandez‐Novell, J. M., J. Arino, S. Vilaro, D. Bellido, and J. J. Guinovart. Role of glucose 6‐phosphate in the translocation of glycogen synthase in rat hepatocytes. Biochem. J. 288: 497–501, 1992.
 90. Fernandez‐Novell, J. M., J. Arino, S. Vilaro, and J. J. Guinovart. Glucose induces the translocation and the aggregation of glycogen synthase in rat hepatocytes. Biochem. J. 281: 443–448, 1992.
 91. Fernandez‐Novell, J. M., D. Bellido, S. Vilaro, and J. J. Guinovart. Glucose induces the translocation of glycogen synthase to the cell cortex in rat hepatocytes. Biochem. J. 321: 227–231, 1997.
 92. Fernandez‐Novell, J. M., A. Roca, D. Bellido, S. Vilaro, and J. J. Guinovart. Translocation and aggregation of hepatic glycogen synthase during the fasted‐to‐refed transition in rats. Eur. J. Biochem. 238: 570–575, 1996.
 93. Ferrans, V. J., B. J. Maron, L. M. Buja, N. Ali, and W. C. Roberts. Intranuclear glycogen deposits in human cardiac muscle cells: ultrastructure and cytochemistry. J. Mol. Cell. Cardio. 7: 373–386, 1975.
 94. Ferrer, J. C., S. Baque, and J. J. Guinovart. Muscle glycogen synthase translocates from the cell nucleus to the cystosol in response to glucose. FEBS Lett. 425: 249–252, 1997.
 95. Field, M. C.. Is there evidence for phospho‐oligosaccharides as insulin mediators? Glycobiology 7: 161–168, 1997.
 96. Fiol, C. J., A. M. Mahrenholz, Y. Wang, R. W. Roeske, and P. J. Roach. Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J. Biol Chem. 262: 14042–14048, 1987.
 97. Fischer, R., M. Koller, M. Flura, S. Mathews, M. A. Strehler‐Page, J. Krebs, J. T. Penniston, E. Carafoli, and E. E. Strehler. Multiple divergent mRNAs code for a single human calmodulin. J. Biol. Chem. 263: 17055–17062, 1988.
 98. Fischer, Y., J. Thomas, L. Sevilla, P. Munoz, C. Becker, G. Holman, I. J. Kozka, M. Palacin, X. Testar, H. Kammermeier, and A. Zorzano. Insulin‐induced recruitment of glucose transporter 4 (GLUT4) and GLUT1 in isolated rat cardiac myocytes. Evidence of the existence of different intracellular GLUT4 vesicle populations. J. Biol. Chem. 272: 7085–7092, 1997.
 99. Flotow, H., P. R. Graves, A. Q. Wang, C. J. Fiol, R. W. Roeske, and P. J. Roach. Phosphate groups as substrate determinants for casein kinase I action. J. Biol. Chem. 265: 14264–14269, 1990.
 100. Flotow, H., and P. J. Roach. Synergistic phosphorylation of rabbit muscle glycogen synthase by cyclic AMP‐dependent protein kinase and casein kinase I. Implications for hormonal regulation of glycogen synthase. J. Biol Chem. 264: 9126–9128, 1989.
 101. Fontana, J. D.. The presence of phosphate in glycogen. FEBS Lett. 109: 85–92, 1980.
 102. Foulkes, J. G., and P. Cohen. The hormonal control of glycogen metabolism. Phosphorylation of protein phosphatase inhibitor‐1 in vivo in response to adrenaline. Eur. J. Biochem. 97: 251–256, 1979.
 103. Francois, J. M., S. Thompson‐Jaeger, J. Skroch, U. Zellenka, W. Spevak, and K. Tatchell. GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae. EMBO J. 11: 87–96, 1992.
 104. Franke, T. F., D. R. Kaplan, L. C. Cantley, and A. Toker. Direct regulation of the Akt proto‐oncogene product by phosphadtidylinositol‐3, 4‐bisphoshate. Science 275: 665–668, 1997.
 105. Franke, T. F., S. I. Yang, T. O. Chan, K. Datta, A. Kazlauskas, D. K. Morrison, D. R. Kaplan, and P. N. Tsichlis. The protein kinase encoded by the Akt proto‐oncogene is a target of the PDGF‐activated phosphatidylinositol 3‐kinase. Cell 81: 727–736, 1995.
 106. Freeh, M., M. Andjelkovic, E. Ingley, K. K. Reddy, J. R. Falck, and B. A. Hemmings. High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272: 8474–8481, 1997.
 107. Frevert, E. U., and B. B. Kahn. Differential effects of constitutively active phosphatidylinositol 3–kinase on glucose transport, glycogen synthase activity, and DNA synthesis in 3T3‐L1 adipocytes. Mol. Cell. Biol. 17: 190–198, 1997.
 108. Friedman, D. L., and J. Larner. Studies on UDPG‐α‐glucan transglucosylase III. Interconversion of two forms of muscle UDPG‐α‐glucan transglucosylase by a phosphorylation‐dephosphorylation reaction sequence. Biochemistry 2: 669–675, 1963.
 109. Furukawa, K., M. Tagaya, M. Inouye, J. Preiss, and T. Fukui. Identification of lysine 15 at the active site in Escherichia coli glycogen synthase. Conservation of Lys‐X‐Gly‐Gly sequence in the bacterial and mammalian enzymes. J. Biol. Chem. 265: 2086–2090, 1990.
 110. Gali, R. R., S. Pugazhenthi, and R. L. Khandelwal. Reciprocal effects of the protein kinase C inhibitors staurosporine and H‐7 on the regulation of glycogen synthase and phosphorylase in the primary culture of hepatocytes. Metabolism 42: 1475–1480, 1993.
 111. Gannon, M. C., and F. Q. Nuttall. Effect of feeding, fasting, and diabetes on liver glycogen synthase activity, protein, and mRNA in rats. Diabetologia 40: 758–763, 1997.
 112. Gannon, M. C., and F. Q. Nuttall. Glycogen in liver: characteristics and biosynthesis. Trends Glycosci. Glycotechnol. 8: 163–194, 1996.
 113. Geddes, R., J. D. Harvey, and P. R. Wills. Hydrodynamic properties of 2‐mercaptoethanol‐modified glycogen. Eur. J. Biochem. 81: 465–172, 1977.
 114. Geddes, R., J. D. Harvey, and P. R. Wills. The molecular size and shape of liver glycogen. Biochem. J. 163: 201–209, 1977.
 115. Ghosh, P., A. C. Heath, M. J. Donahue, and R. A. Masaracchia. Glycogen synthesis in the obliquely striated muscle of Ascaris suum. Eur. J. Biochem. 183: 679–685, 1989.
 116. Gibson, W. B., B. Illingsworth, and D. H. Brown. Studies of glycogen branching enzyme. Preparation and properties of α‐1,4‐glucan‐α‐1,4‐glucan 6‐glycosyltransferase and its action on the characteristic polysaccharide of the liver of children with type IV glycogen storage disease. Biochemistry 10: 4253–4262, 1971.
 117. Goldsmith, E., S. Sprang, and R. Fletterick. Structure of maltoheptaose by difference Fourier methods and a model for glycogen. J. Mol. Biol. 156: 411–427, 1982.
 118. Gomez‐Foix, A. M., W. S. Coats, S. Baque, T. Alam, R. D. Gerard, and C. B. Newgard. Adenovirus‐mediated transfer of the muscle glycogen phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism. J. Biol. Chem. 267: 25129–25134, 1992.
 119. Grand, R. J., S. Shenolikar, and P. Cohen. The amino acid sequence of the delta subunit (calmodulin) of rabbit skeletal muscle phosphorylase kinase. Eur. J. Biochem. 113: 359–367, 1981.
 120. Granner, D., and S. Pilkis. The genes of hepatic glucose metabolism. J. Biol. Chem. 265: 10173–10176, 1990.
 121. Granzow, C., M. Kopun, and H. P. Zimmermann. Role of nuclear glycogen synthase and cytoplasmic UDP glucose pyrophosphorylase in the biosynthesis of nuclear glycogen in HD33 Ehrlich‐Lettre ascites tumor cells. J. Cell. Biol. 89: 475–84, 1981.
 122. Grupe, A., B. Hultgren, A. Ryan, Y. H. Ma, M. Bauer, and T. A. Stewart. Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell 83: 69–78, 1995.
 123. Guinovart, J. J., A. M. Gomez‐Foix, J. Seoane, J. M. Fernandez‐Novell, D. Bellido, and S. Vilaro. Bridging the gap between glucose phosphorylation and glycogen synthesis in the liver. Biochem. Soc. Trans. 25: 157–60, 1997.
 124. Guinovart, J. J., A. Salavert, J. Massague, C. J. Ciudad, E. Salsas, and E. Itarte. Glycogen synthase: a new activity ratio assay expressing a high sensitivity to the phosphorylation state. FEBS Lett. 106: 284–288, 1979.
 125. Gunja‐Smith, Z., J. J. Marshall, C. Mercier, E. E. Smith, and W. J. Whelan. A revision of the Meyer‐Bernfeld model of glycogen and amylopectin. FEBS Lett. 12: 101–104, 1970.
 126. Hanks, S. K., and T. Hunter. The eukaryotic protein kinase super‐family. In: The protein kinase FactsBook: Protein‐Serine Kinases, edited by G. Hardie and S. K. Hanks. San Diego: Academic, 1995, p. 7–47.
 127. Hara, K., K. Yonezawa, H. Sakaue, et al. 1‐Phosphatidylinositol 3‐kinase activity is required for insulin‐stimulated glucose transport but not for RAS activation in CHO cells. Proc. Natl. Acad. Sci. U.S.A. 91: 7415–7419, 1994.
 128. Hardy, T. A., and P. J. Roach. Control of yeast glycogen synthase‐2 by COOH‐terminal phosphorylation. J. Biol. Chem. 268: 23799–23805, 1993.
 129. Hariharan, N., D. Farrelly, D. Hagan, D. Hillyer, C. Arbeeny, T. Sabrah, A. Treloar, K. Brown, S. Kalinowski, and K. Mookhtiar. Expression of human hepatic glucokinase in transgenic mice liver results in decreased glucose levels and reduced body weight. Diabetes 46: 11–16, 1997.
 130. Harmann, B., N. F. Zander, and M. W. Kilimann. Isoform diversity of phosphorylase kinase alpha and beta subunits generated by alternative RNA splicing. J. Biol. Chem. 266: 15631–15637, 1991.
 131. Harris, R. A.. Carbohydrate metabolism I: major metabolic pathways and their control. In: Textbook of Biochemistry with Clinical Correlations (4th ed.), edited by T. M. Devlin. New York: Wiley‐Liss, 1997, p. 267–331.
 132. Hartl, P., E. Olson, T. Dang, and D. J. Forbes. Nuclear assembly with lambda DNA in fractionated Xenopus egg extracts: an unexpected role for glycogen in formation of a higher order chromatin intermediate. J. Cell Biol. 124: 235–248, 1994.
 133. Haschke, R. H., L. M. Heilmeyer, Jr., F. Meyer, and E. H. Fischer. Control of phosphorylase activity in a muscle glycogen particle. 3. Regulation of phosphorylase phosphatase. J. Biol. Chem. 245: 6657–6663, 1970.
 134. Haystead, T. A., A. T. Sim, D. Carling, R. C. Honnor, Y. Tsukitani, P. Cohen, and D. G. Hardie. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature 337: 78–81, 1989.
 135. Heilmeyer, L. M., Jr.. Molecular basis of signal integration in phosphorylase kinase. Biochim. Biophys. Acta 1094: 168–74, 1991.
 136. Heilmyer, L. M., Jr., F. Meyer, R. H. Haschke, and E. H. Fischer. Control of phosphorylase activity in a muscle glycogen particle. II. Activation by calcium. J. Biol. Chem. 245: 6649–6656, 1970.
 137. Hendrickx, J., and P. J. Willems. Genetic deficiencies of the glycogen phosphorylase system. Hum. Genet. 97: 551–556, 1996.
 138. Hiraga, A., and P. Cohen. Phosphorylation of the glycogen‐binding subunit of protein phosphatase‐1G by cyclic‐AMP‐dependent protein kinase promotes translocation of the phosphatase from glycogen to cytosol in rabbit skeletal muscle. Eur. J. Biochem. 161: 763–769, 1986.
 139. Huang, D., I. Farkas, and P. J. Roach. Pho85p, a cyclin‐dependent protein kinase, and the Snflp protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 4357–4365, 1996.
 140. Huang, D., J. Moffatt, W. A. Wilson, L. Moore, C. Cheng, P. J. Roach, and B. Andrews. Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10. Mol. Cell. Biol. 18: 3289–3299, 1998.
 141. Huang, F. L., and W. H. Glinsmann. Separation and characterization of two phosphorylase phosphatase inhibitors from rabbit skeletal muscle. Eur. J. Biochem. 70: 419–426, 1976.
 142. Huang, T. S., and E. G. Krebs. Amino acid sequence of a phosphorylation site in skeletal muscle glycogen synthetase. Biochem. Biophys. Res. Commun. 75: 643–650, 1977.
 143. Hubbard, M. J., and P. Cohen. On target with a new mechanism for the regulation of protein phosphorylation. Trends Biochem. Sci. 18: 172–177, 1993.
 144. Hubbard, M. J., and P. Cohen. Regulation of protein phosphatase‐1G from rabbit skeletal muscle. 1. Phosphorylation by cAMP‐dependent protein kinase at site 2 releases catalytic subunit from the glycogen‐bound holoenzyme. Eur. J. Biochem. 186: 701–709, 1989.
 145. Hubbard, M. J., and P. Cohen. Regulation of protein phosphatase‐1G from rabbit skeletal muscle. 2. Catalytic subunit translocation is a mechanism for reversible inhibition of activity toward glycogenbound substrates. Eur. J. Biochem. 186: 711–716, 1989.
 146. Hudson, J. W., G. B. Golding, and M. M. Crerar. Evolution of allosteric control in glycogen phosphorylase. J. Mol. Biol. 234: 700–721, 1993.
 147. Hurel, S. J., J. J. Rochford, A. C. Borthwick, A. M. Wells, J. R. Vandenheede, D. M. Turnbull, and S. J. Yeaman. Insulin action in cultured human myoblasts: contribution of different signalling pathways to regulation of glycogen synthesis. Biochem. J. 320: 871–7, 1996.
 148. Isakoff, S. J., C. Taha, E. Rose, J. Marcusohn, A. Klip, and E. Y. Skolnik. The inability of phosphatidylinositol 3‐kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin‐stimulated glucose uptake. Proc. Natl. Acad. Sci. U.S.A. 92: 10247–10251, 1995.
 149. Iynedjian, P. B.. Mammalian glucokinase and its gene. Biochem. J. 293: 1–13, 1993.
 150. Iynedjian, P. B., D. Jotterand, T. Nouspikel, M. Asfari, and P. R. Pilot. Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon‐cAMP system. J. Biol. Chem. 264: 21824–21829, 1989.
 151. Iynedjian, P. B., S. Marie, A. Gjinovci, B. Genin, S. P. Deng, L. Buhler, P. Morel, and G. Mentha. Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human liver. Regulation of gene expression in cultured hepatocytes. J. Clin. Invest. 95: 1966–1973, 1995.
 152. James, D., R. Piper, and Slot, J. W.. Insulin stimulation of GLUT‐4 translocation: a model for regulated recycling. Trends Cell Biol. 4: 120–126, 1994.
 153. Jespersen, H. M., E. A. MacGregor, B. Henrissat, M. R. Sierks, and B. Svensson. Starch‐ and glycogen‐debranching and branching enzymes: prediction of structural features of the catalytic (beta/alpha)8‐barrel domain and evolutionary relationship to other amylolytic enzymes. J. Protein Chem. 12: 791–805, 1993.
 154. Johnson, L. N.. Glycogen phosphorylase: control by phosphorylation and allosteric effectors. FASEB J. 6: 2274–2282, 1992.
 155. Johnson, L. N., and D. Barford. Glycogen phosphorylase. The structural basis of the allosteric response and comparison with other allosteric proteins. J. Biol. Chem. 265: 2409–2412, 1990.
 156. Jones, P. F., T. Jakubowicz, and B. A. Hemmings. Molecular cloning of a second form of rac protein kinase. Cell Regul. 2: 1001–1009, 1991.
 157. Jones, P. F., T. Jakubowicz, F. J. Pitossi, F. Maurer, and B. A. Hemmings. Molecular cloning and identification of a serine/threonine protein kinase of the second‐messenger subfamily. Proc. Natl. Acad. Sci. U.S.A. 88: 4171–4175, 1991.
 158. Kaburagi, Y., S. Satoh, H. Tamemoto, R. Yamamoto‐Honda, K. Tobe, K. Veki, T. Yamauchi, E. Kono‐Sugita, H. Sekihara, S. Aizawa, S. W. Cushman, Y. Akanuma, Y. Yazaki, and T. Kadowaki. Role of insulin receptor substrate‐1 and pp60 in the regulation of insulin‐induced glucose transport and GLUT4 translocation in primary adipocytes. J. Biol. Chem. 272: 25839–25844, 1997.
 159. Kahn, B. B.. Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 45: 1644–1654, 1996.
 160. Karasaki, S.. Cytoplasmic and nuclear glycogen synthesis in Novikoff ascites hepatoma cells. J. Ultrastruct. Res. 35: 181–196, 1971.
 161. Kaslow, H. R., D. D. Lesikar, D. Antwi, and A. W. Tan. L‐type glycogen synthase. Tissue distribution and electrophoretic mobility. J. Biol Chem. 260: 9953–9956, 1985.
 162. Kasvinsky, P. J., R. J. Fletterick, and N. B. Madsen. Regulation of the dephosphorylation of glycogen phosphorylase a and synthase b by glucose and caffeine in isolated hepatocytes. Can. J. Biochem. 59: 387–395, 1981.
 163. Katagiri, H., T. Asano, H. Ishihara, K. Inukai, Y. Shibasaki, M. Kikuchi, Y. Yazaki, and Y. Oka. Overexpression of catalytic subunit p110alpha of phosphatidylinositol 3‐kinase increases glucose transport activity with translocation of glucose transporters in 3T3‐L1 adipocytes. J. Biol. Chem. 271: 16987–16990, 1996.
 164. Katz, J., S. Golden, and P. A. Wals. Glycogen synthesis by rat hepatocytes. Biochem. J. 180: 389–402, 1979.
 165. Kennedy, L. D., B. R. Kirkman, J. Lomako, I. R. Rodriguez, and W. J. Whelan. The biogenesis of rabbit muscle glycogen. In Membranes and Muscle, edited by M. C. Berman, W. Gevers, and L. H. Opie. Oxford ICSU/IRL, 1985, p. 65–84.
 166. Kennington, A. S., C. R. Hill, J. Craig, C. Bogardus, I. Raz, H. K. Ortmever, B. C. Hansen, G. Romero, and J. Larner. Low urinary chiro‐inositol excretion in non‐insulin‐dependent diabetes mellitus. N. Engl. J. Med. 323: 373–378, 1990.
 167. Khandelwal, R. L., S. M. Zinman, and E. J. Zebrowski. The effect of streptozotocin‐induced diabetes and of insulin supplementation on glycogen metabolism in rat liver. Biochem. J. 168: 541–548, 1977.
 168. Khatra, B. S., J. L. Chiasson, H. Shikama, J. H. Exton, and T. R. Soderling. Effect of epinephrine and insulin on the phosphorylation of phosphorylase phosphatase inhibitor 1 in perfused rat skeletal muscle. FEBS Lett. 114: 253–256, 1980.
 169. Kilimann, M. W.. Molecular genetics of phosphorylase kinase: cDNA cloning, chromosomal mapping and isoform structure. J. Inherit. Metab. Dis. 13: 435–441, 1990.
 170. Kilimann, M. W., N. F. Zander, C. C. Kuhn, J. W. Crabb, H. E. Meyer, and L. M. Heilmeyer, Jr.. The alpha and beta subunits of phosphorylase kinase are homologous: cDNA cloning and primary structure of the beta subunit. Proc. Natl. Acad. Sci. U.S.A. 85: 9381–9385, 1988.
 171. King, M. M., G. M. Carlson, and B. E. Haley. Photoaffinity labeling of the beta subunit of phosphorylase kinase by 8‐azidoadenosine 5′‐triphosphate and its 2′,3′‐dialdehyde derivative. J. Biol. Chem. 257: 14058–14065, 1982.
 172. Kirkman, B. R., and W. J. Whelan. Glucosamine is a normal component of liver glycogen. FEBS Lett. 194: 6–11, 1986.
 173. Kirkman, B. R., W. J. Whelan, and J. M. Bailey. The distribution of glucosamine in mammalian glycogen from different species, organs and tissues. Biofactors 2: 123–126, 1989.
 174. Klippel, A., C. Reinhard, W. M. Kavanaugh, G. Apell, M. A. Escobedo, and L. T. Williams. Membrane localization of phosphatidylinositol 3‐kinase is sufficient to activate multiple signal‐transducing kinase pathways. Mol. Cell. Biol. 16: 4117–4127, 1996.
 175. Kochan, R. G., D. R. Lamb, E. M. Reimann, and K. K. Schlender. Modified assays to detect activation of glycogen synthase following exercise. Am. J. Physiol. 240 (Endocrinol. Metab. 3): E197–E202, 1981.
 176. Kohn, A. D., S. A. Summers, M. J. Birnbaum, and R. A. Roth. Expression of a constitutively active Akt Ser/Thr kinase in 3T3‐L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J. Biol. Chem. 271: 31372–31378, 1996.
 177. Konishi, H., S. Kuroda, M. Tanaka, H. Matsuzaki, Y. Ono, K. Kameyama, T. Haga, and U. Kikkawa. Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and beta gamma subunits of G proteins. Biochem. Biophys. Res. Commun. 216: 526–534, 1995.
 178. Kopun, M., and C. Granzow. Growth dependence of nuclear glycogen synthesis in mutant HD33 Ehrlich‐Lettre ascites tumor cells. Mol. Cell. Biol. 31: 181–193, 1985.
 179. Kopun, M., C. Granzow, and C. R. Krisman. Comparative study of nuclear and cytoplasmic glycogen isolated from mutant HD33 ascites cells. J. Cell. Biochem. 39: 185–195, 1989.
 180. Krebs, H. A., Williamson, M. W., Bates, M. A., M. A. Page, and R. A. Hawkins. The role of ketone bodies in caloric homeostasis. Adv. Enzyme Regul. 9: 387–409, 1971.
 181. Krisman, C. R., and R. Barengo. A precursor of glycogen biosynthesis: alpha‐1,4‐glucan‐protein. Eur. J. Biochem. 52: 117–123, 1975.
 182. Kurland, I. J., and S. J. Pilkis. Indirect versus direct routes of hepatic glycogen synthesis. FASEB J. 3: 2277–2281, 1989.
 183. Lacoste, E. R., M. C. Miozzo, and J. A. Curtino. A glycogen precursor associated with membrane in retina. Biochem. J. 267: 775–779, 1990.
 184. Larner, J.. Insulin and the stimulation of glycogen synthesis. The road from glycogen structure to glycogen synthase to cyclic AMP‐dependent protein kinase to insulin mediators. Adv. Enzymol. Relat. Areas Mol. Biol. 63: 173–231, 1990.
 185. Larner, J., G. Galasko, K. Cheng, A. A. De Paoli‐Roach, L. Huang, P. Daggy, and J. Kellogg. Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation. Science 206: 1408–1410, 1979.
 186. Larner, J., L. C. Huang, C. F. Schwartz, A. S. Oswald, T. Y. Shen, M. Kinter, G. Z. Tang, and K. Zeller. Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphate contains galactosamine and D‐chiroinositol. Biochem. Biophys. Res. Commun. 151: 1416–1426, 1988.
 187. Lavan, B. E., W. S. Lane, and G. E. Lienhard. The 60‐kDa phosphotyrosine protein in insulin‐treated adipocytes is a new member of the insulin receptor substrate family. J. Biol. Chem. 272: 11439–11443, 1997.
 188. Lavoie, L., D. Dimitrakoudis, A. Marette, B. Annabi, A. Klip, M. Vranic, and G. van de Werve. Opposite effects of hyperglycemia and insulin deficiency on liver glycogen synthase phosphatase activity in the diabetic rat. Diabetes 42: 363–366, 1993.
 189. Lawrence, J. C., Jr., J. F. Hiken, A. A. De Paoli‐Roach, and P. J. Roach. Hormonal control of glycogen synthase in rat hemidiaphragms. Effects of insulin and epinephrine on the distribution of phosphate between two cyanogen bromide fragments. J. Biol. Chem. 258: 10710–10719, 1983.
 190. Lawrence, J. C., Jr., and P. J. Roach. New insights into the role and mechanism of glycogen synthase activation by insulin. Diabetes 46: 541–547, 1997.
 191. Lawrence, J. C., Jr., A. V. Skurat, P. J. Roach, I. Azpiazu, and J. Manchester. Glycogen synthase: activation by insulin and effect of transgenic overexpression in skeletal muscle. Biochem. Soc. Trans. 25: 14–19, 1997.
 192. Lazar, D. F., J. J. Knez, M. E. Medof, P. Cuatrecasas, and A. R. Saltiel. Stimulation of glycogen synthesis by insulin in human ery‐throleukemia cells requires the synthesis of glycosyl‐phosphatidylinositol. Proc. Natl. Acad. Sci. U.S.A. 91: 9665–9669, 1994.
 193. Lazar, D. F., R. J. Wiese, M. J. Brady, C. C. Mastick, S. B. Waters, K. Yamauchi, J. E. Pessin, P. Cuatrecasas, and A. R. Saltiel. Mitogen‐activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin. J. Biol. Chem. 270: 20801–20807, 1995.
 194. Lenburg, M. E., and E. K. O'Shea. Signaling phosphate starvation. Trends Biochem. Sci. 21: 383–387, 1996.
 195. Lew, J., Q. Q. Huang, Z. Qi, R. J. Winkfein, R. Aebersold, T. Hunt, and J. H. Wang. A brain‐specific activator of cyclin‐dependent kinase 5. Nature 371: 423–426, 1994.
 196. Lin, A., Mu, J. and Roach, P. J. (1999) Self‐glucosylation of glycozenur, the initiator of glycogen biosynthesis, involves an intersubunit reaction Arch. Biochem. Biophys. 363, 167–170.
 197. Liu, W., M. L. de Castro, J. Takrama, P. T. Bilous, T. Vinayagamoorthy, N. B. Madsen, and R. C. Bleackley. Molecular cloning, sequencing, and analysis of the cDNA for rabbit muscle glycogen debranching enzyme. Arch. Biochem. Biophys. 306: 232–239, 1993.
 198. Lomako, J., W. M. Lomako, B. R. Kirkman, and W. J. Whelan. The role of phosphate in muscle glycogen. Biofactors 4: 167–171, 1994.
 199. Lomako, J., W. M. Lomako, and W. J. Whelan. A self‐glucosylating protein is the primer for rabbit muscle glycogen biosynthesis [published erratum appears in FASEB J. 1989: 1873]. FASEB J. 2: 3097–3103, 1988.
 200. Lomako, J., W. M. Lomako, and W. J. Whelan. Glycogen metabolism in quail embryo muscle. The role of the glycogenin primer and the intermediate proglycogen. Eur. J. Biochem. 234: 343–349, 1995.
 201. Lomako, J., W. M. Lomako, and W. J. Whelan. Proglycogen: a low‐molecular‐weight form of muscle glycogen. FEBS Lett. 279: 223–228, 1991.
 202. Lomako, J., W. M. Lomako, and W. J. Whelan. Substrate specificity of the autocatalytic protein that primes glycogen synthesis. FEBS Lett. 264: 13–16, 1990.
 203. Lomako, J., W. M. Lomako, and W. J. Whelan. The substrate specificity of isoamylase and the preparation of apo‐glycogenin. Carbohydr. Res. 227: 331–338, 1992.
 204. Lomako, J., W. M. Lomako, W. J. Whelan, R. S. Dombro, J. T. Neary, and M. D. Norenberg. Glycogen synthesis in the astrocyte: from glycogenin to proglycogen to glycogen. FASEB J. 7: 1386–1393, 1993.
 205. Lomako, J., W. M. Lomako, W. J. Whelan, and R. B. Marchase. Glycogen contains phosphodiester groups that can be introduced by UDPglucose: glycogen glucose 1‐phosphotransferase. FEBS Lett. 329: 263–267, 1993.
 206. Lomako, J., K. Mazuruk, W. M. Lomako, M. D. Alonso, W. J. Whelan, and I. R. Rodriguez. The human intron‐containing gene for glycogenin maps to chromosome 3, band q24. Genomics 33: 519–522, 1996.
 207. Lomako, J., and W. J. Whelan. The occurrence of serine phosphate in glycogenin: a possible regulatory site. Biofactors 1: 261–264, 1988.
 208. Longenecker, K. L., P. J. Roach, and T. D. Hurley. Three‐dimensional structure of mammalian casein kinase I: molecular basis for phosphate recognition. J. Mol. Biol. 257: 618–631, 1996.
 209. Lowe, E. D., M. E. M. Noble, V. T. Shamnaki, N. G. Oikonomakos, D. J. Owen, and L. N. Johnson. The crystal structure of a phosphorylase kinase peptide substrate complex: kinase substrate recognition. EMBO J. 16: 6646–6658, 1997.
 210. MacKintosh, C., D. G. Campbell, A. Hiraga, and P. Cohen. Phosphorylation of the glycogen‐binding subunit of protein phosphatase‐1G in response to adrenalin. FEBS Lett. 234: 189–194, 1988.
 211. Madsen, N. B.. Glycogen phosphorylase: control by phosphorylation. In: The Enzymes (3rd ed.) edited by P. D. Boyer and E. G. Krebs. Orlando, FL: Academic, 1986, vol. 17, p. 366–394.
 212. Madsen, N. B., and C. F. Cori. The binding of glycogen and phosphorylase. J. Biol. Chem. 233: 1251–1256, 1958.
 213. Magnuson, M. A.. Glucokinase gene structure. Functional implications of molecular genetic studies. Diabetes 39: 523–527, 1990.
 214. Magnuson, M. A., T. L. Andreone, R. L. Printz, S. Koch, and D. K. Granner. Rat glucokinase gene: structure and regulation by insulin. Proc. Natl. Acad. Sci. U.S.A. 86: 4838–4842, 1989.
 215. Mahrenholz, A. M., Y. H. Wang, and P. J. Roach. Catalytic site of rabbit glycogen synthase isozymes. Identification of an active site lysine close to the amino terminus of the subunit. J. Biol. Chem. 263: 10561–10567, 1988.
 216. Manchester, J., A. V. Skurat, P. Roach, S. D. Hauschka, and J. C. Lawrence, Jr.. Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle. Proc. Natl. Acad. Sci. U.S.A. 93: 10707–10711, 1996.
 217. Manzella, S. M., L. Roden, and E. Meezan. A biphasic radiometric assay of glycogenin using the hydrophobic acceptor N‐dodecyl‐beta‐D‐maltoside. Anal. Biochem. 216: 383–391, 1994.
 218. Manzella, S. M., L. Roden, and E. Meezan. Dodecyl‐beta‐D‐maltoside as a substrate for glucosyl and xylosyl transfer by glycogenin. Glycobiology 5: 263–271, 1995.
 219. Martin, S. S., T. Haruta, A. J. Morris, A. Klippel, L. T. Williams, and J. M. Olefsky. Activated phosphatidylinositol 3‐kinase is sufficient to mediate actin rearrangement and GLUT4 translocation in 3T3‐L1 adipocytes. J. Biol. Chem. 271: 17605–17608, 1996.
 220. Massillon, D., N. Barzilai, W. Chen, M. Hu, and L. Rossetti. Glucose regulates in vivo glucose‐6‐phosphatase gene expression in the liver of diabetic rats. J. Biol. Chem. 271: 9871–9874, 1996.
 221. Massillon, D., M. Bollen, H. De Wulf, K. Overloop, F. Vanstapel, P. Van Hecke, and W. Stalmans. Demonstration of a glycogen/glucose 1‐phosphate cycle in hepatocytes from fasted rats. Selective inactivation of phosphorylase by 2‐deoxy‐2‐fluoro‐alpha‐D‐glucopyranosyl fluoride. J. Biol. Chem. 270: 19351–19356, 1995.
 222. Mato, J. M., K. L. Kelly, A. Abler, L. Jarett, B. E. Corkey, J. A. Cashel, and D. Zopf. Partial structure of an insulin‐sensitive glycophospholipid. Biochem. Biophys. Res. Commun. 146: 764–770, 1987.
 223. Measday, V., L. Moore, J. Ogas, M. Tyers, and B. Andrews. The PCL2 (ORFD)‐PH085 cyclin‐dependent kinase complex: a cell cycle regulator in yeast. Science 266: 1391–1395, 1994.
 224. Measday, V., L. Moore, R. Retnakaran, J. Lee, M. Donoviel, A. M. Neiman, and B. Andrews. A family of cyclin‐like proteins that interact with the Pho85 cyclin‐dependent kinase. Mol. Cell. Biol. 17: 1212–1223, 1997.
 225. Melendez‐Hevia, E., T. G. Waddell, and E. D. Shelton. Optimization of molecular design in the evolution of metabolism: the glycogen molecule. Biochem. J. 295: 477–483, 1993.
 226. Meyer, F., L. M. Heilmeyer, Jr., R. H. Haschke, and E. H. Fischer. Control of phosphorylase activity in a muscle glycogen particle. I. Isolation and characterization of the protein‐glycogen complex. J. Biol. Chem. 245: 6642–6648, 1970.
 227. Miller, T. B., Jr.. Effects of diabetes on glucose regulation of enzymes involved in hepatic glycogen metabolism. Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E13–E19, 1978.
 228. Miller, T. B., Jr.. Glucose activation of liver glycogen synthase. Insulin‐mediated restoration of glucose effect in diabetic rats is blocked by protein synthesis inhibitor. Biochim. Biophys. Acta 583: 36–46, 1979.
 229. Miozzo, M. C., E. R. Lacoste, and J. A. Curtino. Characterization of the proteoglycogen fraction non‐extractable from retina by trichloroacetic acid. Biochem. J. 260: 287–289, 1989.
 230. Mitchell, J. W., R. L. Mellgren, and J. A. Thomas. Phosphorylation of heart glycogen synthase by cAMP‐dependent protein kinase. Regulatory effects of ATP. J. Biol. Chem. 255: 10368–10374, 1980.
 231. Mithieux, G., H. Vidal, C. Zitoun, N. Bruni, N. Daniele, and C. Minassian. Glucose‐6‐phosphatase mRNA and activity are increased to the same extent in kidney and liver of diabetic rats. Diabetes 45: 891–896, 1996.
 232. Monod, J., J. Wyman, and J.‐P. Changeux. On the nature of allosteric transitions: a possible model. J. Mol. Biol. 12: 88–118, 1965.
 233. Moorhead, G., C. MacKintosh, N. Morrice, and P. Cohen. Purification of the hepatic glycogen‐associated form of protein phosphatase‐1 by microcystin‐Sepharose affinity chromatography. FEBS Lett. 362: 101–105, 1995.
 234. Moule, S. K., and R. M. Denton. Multiple signaling pathways involved in the metabolic effects of insulin. Am. J. Cardio. 80: 41A–49A, 1997.
 235. Moule, S. K., G. I. Welsh, N. J. Edgell, E. J. Foulstone, C. G. Proud, and R. M. Denton. Regulation of protein kinase B and glycogen synthase kinase‐3 by insulin and beta‐adrenergic agonists in rat epididymal fat cells. Activation of protein kinase B by wortmannin‐sensitive and‐insensitive mechanisms. J. Biol. Chem. 272: 7713–7719, 1997.
 236. Moxham, C. M., A. Tabrizchi, R. J. Davis, and C. C. Malbon. Jun N‐terminal kinase mediates activation of skeletal muscle glycogen synthase by insulin in vivo. J. Biol. Chem. 271: 30765–30773, 1996.
 237. Mu, J., C. Cheng, and P. J. Roach. Initiation of glycogen synthesis in yeast. Requirement of multiple tyrosine residues for function of the self‐glucosylating Glg proteins in vivo. J. Biol. Chem. 271: 26554–26560, 1996.
 238. Mu, J., A. V. Skurat, and P. J. Roach. Glycogenin‐2, a novel self‐glucosylating protein involved in liver glycogen biosynthesis. J. Biol. Chem. 272: 27589–27597, 1997.
 239. Munoz, P., S. Mora, L. Sevilla, P. Kaliman, E. Tomas, A. Guma, X. Testar, M. Palacin, and A. Zorzano. Expression and insulin‐regulated distribution of caveolin in skeletal muscle. Caveolin does not colocalize with GLUT4 in intracellular membranes. J. Biol. Chem. 271: 8133–8139, 1996.
 240. Munoz, P., M. Rosemblatt, X. Testar, M. Palacin, G. Thoidis, P. F. Pilch, and A. Zorzano. The T‐tubule is a cell‐surface target for insulin‐regulated recycling of membrane proteins in skeletal muscle. Biochem. J. 312: 393–400, 1995.
 241. Murata, T., H. Katagiri, H. Ishihara, Y. Shibasaki, T. Asano, Y. Toyoda, B. Pekiner, C. Pekiner, I. Miwa, and Y. Oka. Co‐localization of glucokinase with actin filaments. FEBS Lett. 406: 109–113, 1997.
 242. Nakano, K., P. K. Hwang, and R. J. Fletterick. Complete cDNA sequence for rabbit muscle glycogen phosphorylase. FEBS Lett. 204: 283–287, 1986.
 243. Nakielny, S., D. G. Campbell, and P. Cohen. The molecular mechanism by which adrenalin inhibits glycogen synthesis. Eur. J. Biochem. 199: 713–722, 1991.
 244. Nave, B. T., R. J. Haigh, A. C. Hayward, K. Siddle, and P. R. Shepherd. Compartment‐specific regulation of phosphoinositide 3‐kinase by platelet‐derived growth factor and insulin in 3T3‐L1 adipocytes. Biochem. J. 318: 55–60, 1996.
 245. Newgard, C. B., P. K. Hwang, and R. J. Fletterick. The family of glycogen phosphorylases: structure and function. Crit. Rev. Biochem. Mol. Biol. 24: 69–99, 1989.
 246. Newgard, C. B., D. R. Littman, C. van Genderen, M. Smith, and R. J. Fletterick. Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes. J. Biol. Chem. 263: 3850–3857, 1988.
 247. Nimmo, H. G., C. G. Proud, and P. Cohen. The purification and properties of rabbit skeletal muscle glycogen synthase. Eur. J. Biochem. 68: 21–30, 1976.
 248. Niswender, K. D., C. Postic, M. Shiota, T. L. Jetton, and M. A. Magnuson. Effects of altered glucokinase gene copy number on blood glucose homoeostasis. Biochem. Soc. Trans. 25: 113–117, 1997.
 249. Niswender, K. D., M. Shiota, C. Postic, A. D. Cherrington, and M. A. Magnuson. Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism. J. Biol. Chem. 272: 22570–22575, 1997.
 250. Norcum, M. T., D. A. Wilkinson, M. C. Carlson, J. F. Hainfeld, and G. M. Carlson. Structure of phosphorylase kinase. A three‐dimensional model derived from stained and unstained electron micrographs. J. Mol. Biol. 241: 94–102, 1994.
 251. Nur, T., I. Sela, N. J. Webster, and Z. Madar. Starvation and refeeding regulate glycogen synthase gene expression in rat liver at the posttranscriptional level. J. Nutr. 125: 2457–2462, 1995.
 252. Nuttall, F. Q., and M. C. Gannon. Allosteric regulation of glycogen synthase in liver. A physiological dilemma. J. Biol. Chem. 268: 13286–13290, 1993.
 253. Nuttall, F. Q., M. C. Gannon, G. Bai, and E. Y. Lee. Primary structure of human liver glycogen synthase deduced by cDNA cloning. Arch. Biochem. Biophys. 311: 443–449, 1994.
 254. O'Doherty, R. M., D. L. Lehman, J. Seoane, A. M. Gomez‐Foix, J. J. Guinovart, and C. B. Newgard. Differential metabolic effects of adenovirus‐mediated glucokinase and hexokinase I over‐expression in rat primary hepatocytes. J. Biol. Chem. 271: 20524–20530, 1996.
 255. Ohyumi, M., and S. Takano. Intranuclear synthesized and native glycogen particles in human gastric cancer: ultrastructure and histochemistry. Histochemistry 50: 239–250, 1977.
 256. Okada, T., Y. Kawano, T. Sakakibara, O. Hazeki, and M. Ui. Essential role of phosphatidylinositol 3‐kinase in insulin‐induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J. Biol. Chem. 269: 3568–3573, 1994.
 257. Olson, A. L., and J. E. Pessin. Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. Annu. Rev. Nutr. 16: 235–256, 1996.
 258. Oron, Y., R. Cardell, and J. Larner. Nuclear glycogen synthase—an artifact of preparation. FEBS Lett. 118: 255–258, 1980.
 259. Ortmeyer, H. K., N. L. Bodkin, K. Lilley, J. Larner, and B. C. Hansen. Chiroinositol deficiency and insulin resistance. I. Urinary excretion rate of chiroinositol is directly associated with insulin resistance in spontaneously diabetic rhesus monkeys. Endocrinology 132: 640–564, 1993.
 260. Ostlund, R. E., Jr., J. B. McGill, I. Herskowitz, D. M. Kipnis, J. V. Santiago, and W. R. Sherman. D‐Chiro‐inositol metabolism in diabetes mellitus. Proc. Natl. Acad. Sci. U.S.A. 90: 9988–9992, 1993.
 261. Parker, P. J., F. B. Caudwell, and P. Cohen. Glycogen synthase from rabbit skeletal muscle; effect of insulin on the state of phosphorylation of the seven phosphoserine residues in vivo. Eur. J. Biochem. 130: 227–234, 1983.
 262. Parker, P. J., N. Embi, F. B. Caudwell, and P. Cohen. Glycogen synthase from rabbit skeletal muscle. State of phosphorylation of the seven phosphoserine residues in vivo in the presence and absence of adrenaline. Eur. J. Biochem. 124: 47–55, 1982.
 263. Parodi, A. J., J. Mordoh, C. R. Krisman, and L. F. Leloir. In vitro synthesis of particulate glycogen from uridine diphosphate glucose. Arch. Biochem. Biophys. 132: 111–117, 1969.
 264. Parsa, R., J. F. Decaux, P. Bossard, B. R. Robey, M. A. Magnuson, D. K. Granner, and J. Girard. Induction of the glucokinase gene by insulin in cultured neonatal rat hepatocytes. Relationship with DNase‐I hypersensitive sites and functional analysis of a putative insulin‐response element. Eur. J. Biochem. 236: 214–221, 1996.
 265. Patti, M. E., X. J. Sun, J. C. Bruening, E. Araki, M. A. Lipes, M. F. White, and C. R. Kahn. 4PS/insulin receptor substrate (IRS)‐2 is the alternative substrate of the insulin receptor in IRS‐1‐deficient mice. J. Biol. Chem. 270: 24670–24673, 1995.
 266. Pessin, J. E., and G. I. Bell. Mammalian facilitative glucose transporter family: structure and molecular regulation. Annu. Rev. Physiol. 54: 911–930, 1992.
 267. Pickett‐Gies, C. A., and D. A. Walsh. Phosphorylase kinase. In: The Enzymes, edited by, P. D. Boyer and E. G. Krebs. Orlando, FL: Academic, Press, 1986, vol. 17, p. 395–495.
 268. Picton, C., A. Aitken, T. Bilham, and P. Cohen. Multisite phosphorylation of glycogen synthase from rabbit skeletal muscle. Organisation of the seven sites in the polypeptide chain. Eur. J. Biochem. 124: 37–45, 1982.
 269. Picton, C., J. Woodgett, B. Hemmings, and P. Cohen. Multisite phosphorylation of glycogen synthase from rabbit skeletal muscle. Phosphorylation of site 5 by glycogen synthase kinase‐5 (casein kinase‐II) is a prerequisite for phosphorylation of sites 3 by glycogen synthase kinase‐3. FEBS Lett. 150: 191–196, 1982.
 270. Piras, R., L. B. Rothman, and E. Cabib. Regulation of muscle glycogen synthetase by metabolites. Differential effects on the I and D forms. Biochemistry 7: 56–66, 1968.
 271. Pitcher, J., C. Smythe, D. G. Campbell, and P. Cohen. Identification of the 38‐kDa subunit of rabbit skeletal muscle glycogen synthase as glycogenin. Eur. J. Biochem. 169: 497–502, 1987.
 272. Pitcher, J., C. Smythe, and P. Cohen. Glycogenin is the priming glucosyltransferase required for the initiation of glycogen biogenesis in rabbit skeletal muscle. Eur. J. Biochem. 176: 391–395, 1988.
 273. Plyte, S. E., K. Hughes, E. Nikolakaki, B. J. Pulverer, and J. R. Woodgett. Glycogen synthase kinase‐3: functions in oncogenesis and development. Biochem. Biophys. Acta 1114: 147–62, 1992.
 274. Polishchuk, S. V., N. R. Brandt, H. E. Meyer, M. Varsanyi, and L. M. Heilmeyer, Jr.. Does phosphorylase kinase control glycogen biosynthesis in skeletal muscle? FEBS Lett. 362: 271–275, 1995.
 275. Poulter, L., S. G. Ang, B. W. Gibson, D. H. Williams, C. F. Holmes, F. B. Caudwell, J. Pitcher, and P. Cohen. Analysis of the in vivo phosphorylation state of rabbit skeletal muscle glycogen synthase by fast‐atom‐bombardment mass spectrometry. Eur. J. Biochem. 175: 497–510, 1988.
 276. Preiss, J., and T. Romeo. Molecular biology and regulatory aspects of glycogen biosynthesis in bacteria. Prog. Nucleic Acid Res. Mol. Biol. 47: 299–329, 1994.
 277. Preiss, J., and T. Romeo. Physiology, biochemistry and genetics of bacterial glycogen synthesis. Adv. Microb. Physiol. 30: 183–238, 1989.
 278. Preiss, J., and D. A. Walsh. The comparative biochemistry of glycogen and starch. In: Biology of Carbohydrates, edited by V. Ginsburg and P. Robbins. New York. Wiley, 1981, vol. 1, p. 199–314.
 279. Printen, J. A., M. J. Brady, and A. R. Saltiel. PTG, a protein phosphatase 1‐binding protein with a role in glycogen metabolism. Science 275: 1475–1478, 1997.
 280. Pugazhenthi, S., and R. L. Khandelwal. Kinases and phosphatase of hepatic glycogen metabolism during fasted to refed transition in normal and streptozotocin‐induced diabetic rats. Biochem. Int. 23: 515–524, 1991.
 281. Pugazhenthi, S., and R. L. Khandelwal. Regulation of glycogen synthase activation in isolated hepatocytes. Mol. Cell. Biochem. 149–150: 95–101, 1995.
 282. Pugazhenthi, S., B. Yu, R. R. Gali, and R. L. Khandelwal. Differential effects of calyculin A and okadaic acid on the glucose‐induced regulation of glycogen synthase and phosphorylase activities in cultured hepatocytes. Biochim. Biophys. Acta 1179: 271–276, 1993.
 283. Qi, Z., D. Tang, I. Matsuura, K. Y. Lee, X. Zhu, Q. Q. Huang, and J. H. Wang. Regulatory properties of neuronal cdc2‐like kinase. Mol. Cell. Biochem. 149–150: 35–39, 1995.
 284. Quon, M. J., H. Chen, B. L. Ing, M. L. Liu, M. J. Zarnowski, K. Yonezawa, M. Kasuga, S. W. Cushman, and S. I. Taylor. Roles of 1‐phosphatidylinositol 3‐kinase and ras in regulating translocation of GLUT4 in transfected rat adipose cells. Mol. Cell. Biol. 15: 5403–5411, 1995.
 285. Ragolia, L., and N. Begum. The effect of modulating the glycogen‐associated regulatory subunit of protein phosphatase‐1 on insulin action in rat skeletal muscle cells. Endocrinology 138: 2398–2404, 1997.
 286. Ramakrishna, S., and W. B. Benjamin. Insulin action rapidly decreases multifunctional protein kinase activity in rat adipose tissue. J. Biol. Chem. 263: 12677–12681, 1988.
 287. Rao, P. V., S. Pugazhenthi, and R. L. Khandelwal. The effects of streptozotocin‐induced diabetes and insulin supplementation on expression of the glycogen phosphorylase gene in rat liver. J. Biol. Chem. 270: 24955–24960, 1995.
 288. Rea, S., and D. E. James. Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 46: 1667–1677, 1997.
 289. Ren, J. M., B. A. Marshall, E. A. Gulve, J. Gao, D. W. Johnson, J. O. Holloszy, and M. Mueckler. Evidence from transgenic mice that glucose transport is rate‐limiting for glycogen deposition and glycolysis in skeletal muscle. J. Biol. Chem. 268: 16113–16115, 1993.
 290. Rencurel, F., G. Waeber, B. Antoine, F. Rocchiccioli, P. Maulard, J. Girard, and A. Leturque. Requirement of glucose metabolism for regulation of glucose transporter type 2 (GLUT2) gene expression in liver. Biochem. J. 314: 903–990, 1996.
 291. Rencurel, F., G. Waeber, C. Bonny, B. Antoine, P. Maulard, J. Girard, and A. Leturque. cAMP prevents the glucose‐mediated stimulation of GLUT2 gene transcription in hepatocytes. Biochem. J. 322: 441–448, 1997.
 292. Ricort, J. M., J. F. Tanti, E. Van Obberghen, and Y. Le Marchand‐Brustel. Different effects of insulin and platelet‐derived growth factor on phosphatidylinositol 3‐kinase at the subcellular level in 3T3‐L1 adipocytes. A possible explanation for their specific effects on glucose transport. Eur. J. Biochem. 239: 17–22, 1996.
 293. Roach, P. J.. Control of glycogen synthase by hierarchal protein phosphorylation. FASEB J. 4: 2961–2968, 1990.
 294. Roach, P. J.. Liver glycogen synthase. In: The Enzymes (3rd ed.) edited by P. D. Boyer and E. G. Krebs. Orlando, FL. Academic, 1986, vol. 17, p. 499–539.
 295. Roach, P. J.. Multisite and hierarchal protein phosphorylation. J. Biol. Chem. 266: 14139–14142, 1991.
 296. Roach, P. J., A. A. De Paoli‐Roach, and J. Larner. Ca2+‐stimulated phosphorylation of muscle glycogen synthase by phosphorylase b kinase. J. Cyclic Nucleotide Res. 4: 245–257, 1978.
 297. Roach, P. J., and J. Larner. Covalent phosphorylation in the regulation of glycogen synthase activity. Mol. Cell. Biochem. 15: 179–200, 1977.
 298. Roach, P. J., and J. Larner. Rabbit skeletal muscle glycogen synthase. II. Enzyme phosphorylation state and effector concentrations as interacting control parameters. J. Biol. Chem. 251: 1920–1925, 1976.
 299. Roach, P. J., and J. Larner. Regulation of glycogen synthase: a relation of enzymic properties with biological function. Trends Biochem. Sci. 1: 110–112, 1976.
 300. Roach, P. J., and P. J. Skurat. Self‐glucosylating initiator proteins and their role in glycogen biosynthesis. Prog. Nucleic Acid Res. Mol. Biol. 57: 289–316, 1997.
 301. Roach, P. J., Y. Takeda, and J. Larner. Rabbit skeletal muscle glycogen synthase. 1. Relationship between phosphorylation state and kinetic properties. J. Biol. Chem. 251: 1913–1919, 1976.
 302. Rodriguez, I. R., and W. J. Whelan. A novel glycosyl‐amino acid linkage: rabbit‐muscle glycogen is covalently linked to a protein via tyrosine. Biochem. Biophys. Res. Commun. 132: 829–836, 1985.
 303. Romero, G., and J. Larner. Insulin mediators and the mechanism of insulin action. Adv. Pharmacol. 24: 21–50, 1993.
 304. Romero, P. A., E. E. Smith, and W. J. Whelan. Glucosamine as a substitute for glucose in glycogen metabolism. Biochem. Int. 1: 1–9, 1980.
 305. Rowen, D. W., Meinke, and D. C. La Porte. GLC3 and GHA1 of Saccharomyces cerevisiae are allelic and encode the glycogen branching enzyme. Mol. Cell. Biol. 12: 22–29, 1992.
 306. Rulfs, J., S. R. Jaspers, A. K. Garnache, and T. B. Miller, Jr.. Phosphorylase synthesis in diabetic hepatocytes and cardiomyocytes. Am. J. of Physiol. 257 (Endocrinol. Metab. 20): E74–E80, 1989.
 307. Rybicka, K. K.. Glycosomes—the organelles of glycogen metabolism. Tissue Cell 28: 253–265, 1996.
 308. Rylatt, D. B., A. Aitken, T. Bilham, G. D. Condon, N. Embi, and P. Cohen. Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase‐3, and extension of the N‐terminal sequence containing the site phosphorylated by phosphorylase kinase. Eur. J. Biochem. 107: 529–537, 1980.
 309. Sakaue, H., K. Hara, T. Noguchi, T. Matozaki, K. Kotani, W. Ogawa, K. Yonezawa, M. D. Waterfield, and M. Kasuga. Ras‐independent and wortmannin‐sensitive activation of glycogen synthase by insulin in Chinese hamster ovary cells. J. Biol. Chem. 270: 11304–11309, 1995.
 310. Saltiel, A. R.. Diverse signaling pathways in the cellular actions of insulin. Am. J. Physiol. 270 (Endocrinol. Metab. 33): E375–85, 1996.
 311. Saltiel, A. R.. Structural and functional roles of glycosylphospho‐inositides. Subcell. Biochem. 26: 165–85, 1996.
 312. Saltiel, A. R., A. Doble, S. Jacobs, and P. Cuatrecasas. Putative mediators of insulin action regulate hepatic acetyl CoA carboxylase activity. Biochem. Biophys. Res. Commun. 110: 789–795, 1983.
 313. Saltiel, A. R., M. I. Siegel, S. Jacobs, and P. Cuatrecasas. Putative mediators of insulin action: regulation of pyruvate dehydrogenase and adenylate cyclase activities. Proc. Natl. Acad. Sci. U.S.A. 79: 3513–3517, 1982.
 314. Schlender, K. K., and C. M. Doster. Purification and some regulatory properties of glycogen synthase 1 from rabbit renal medulla. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 71: 423–430, 1982.
 315. Schulz, A. R.. Control analysis of muscle glycogen metabolism. Arch. Biochem. Biophys. 353: 172–180, 1998.
 316. Seals, J. R., and L. Jarett. Activation of pyruvate dehydrogenase by direct addition of insulin to an isolated plasma membrane/mitochondria mixture: evidence for generated of insulin's second messenger in a subcellular system. Proc. Natl. Acad. Sci. U.S.A. 77: 77–81, 1980.
 317. Sen Gupta, B., F. Friedberg, and S. D. Detera‐Wadleigh. Molecular analysis of human and rat calmodulin complementary DNA clones. Evidence for additional active genes in these species. J. Biol. Chem. 262: 16663–16670, 1987.
 318. Seoane, J., A. M. Gomez‐Foix. R. M. O'Doherty, C. Gomez‐Ara, C. B. Newgard, and J. J. Guinovart. Glucose 6‐phosphate produced by glucokinase, but not hexokinase I, promotes the activation of hepatic glycogen synthase. J. Biol. Chem. 271: 23756–23760, 1996.
 319. Seoane, J., K. Trinh, R. M. O'Doherty, A. M. Gomez‐Foix, A. J. Lange, C. B. Newgard, and J. J. Guinovart. Metabolic impact of adenovirus‐mediated overexpression of the glucose‐6‐phosphatase catalytic subunit in hepatocytes. J. Biol. Chem. 272: 26972–2697, 1997.
 320. Shen, L. C., C. Villar‐Palasi, and J. Larner. Hormonal alteration of protein kinase sensitivity to 3′,5′‐cyclic AMP. Physiol. Chem. Phys. 2: 536–544, 1970.
 321. Sheorain, V. S., B. S. Khatra, and T. R. Soderling. Hormonal regulation of glycogen synthase phosphorylation in rabbit skeletal muscle. J. Biol. Chem. 257: 3462–3470, 1982.
 322. Shepherd, P. R., B. T. Nave, J. Rincon, R. J. Haigh, E. Foulstone, C. Proud, J. R. Zierath, K. Siddle, and H. Wallberg‐Henriksson. Involvement of phosphoinositide 3‐kinase in insulin stimulation of MAP‐kinase and phosphorylation of protein kinase‐B in human skeletal muscle: implications for glucose metabolism. Diabetologia 40: 1172–1177, 1997.
 323. Shepherd, P. R., B. T. Nave, J. Rincon, L. A. Nolte, A. P. Bevan, K. Siddle, J. R. Zierath, and H. Wallberg‐Henriksson. Differential regulation of phosphoinositide 3‐kinase adapter subunit variants by insulin in human skeletal muscle. J. Biol. Chem. 272: 19000–19007, 1997.
 324. Shepherd, P. R., B. T. Nave, and K. Siddle. Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3‐L1 adipocytes: evidence for the involvement of phosphoinositide 3‐kinase and p70 ribosomal protein‐S6 kinase. Biochem. J. 305: 25–28, 1995.
 325. Shulman, G. I., and B. R. Landau. Pathways of glycogen repletion. Physiol. Rev. 72: 1019–1035, 1992.
 326. Shulman, R. G., G. Bloch, and D. L. Rothman. In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis. Proc. Natl. Acad. Sci. U.S.A. 92: 8535–8542, 1995.
 327. Shulman, R. G., and D. L. Rothman. Enzymatic phosphorylation of muscle glycogen synthase: a mechanism for maintenance of metabolic homeostasis. Proc. Natl. Acad. Sci. U.S.A. 93: 7491–7495, 1996.
 328. Sivaramakrishnan, S., C. W. High, and D. A. Walsh. Regulation of cardiac glycogen synthase by phosphorylation: catalysis of inactivation by cAMP‐dependent and cAMP‐independent protein kinases and comparison with the phosphorylation of the skeletal muscle enzyme. Arch. Biochem. Biophys. 214: 311–325, 1982.
 329. Skurat, A. V., Y. Cao, and P. J. Roach. Glucose control of rabbit skeletal muscle glycogenin expressed in COS cells. J. Biol. Chem. 268: 14701–14707, 1993.
 330. Skurat, A. V., S.‐S. Lim, and P. J. Roach. Glycogen biogenesis in Rat1 fibroblasts expressing rabbit muscle glycogenin. Eur. J. Biochem., 245, 147–55, 1997.
 331. Skurat, A. V., H. L. Peng, H. Y. Chang, J. F. Cannon, and P. J. Roach. Rate‐determining steps in the biosynthesis of glycogen in COS cells. Arch. Biochem. Biophys. 328: 283–288, 1996.
 332. Skurat, A. V., and P. J. Roach. Multiple mechanisms for the phosphorylation of C‐terminal regulatory sites in rabbit muscle glycogen synthase expressed in COS cells. Biochem. J. 313: 45–50, 1996.
 333. Skurat, A. V., and P. J. Roach. Phosphorylation of sites 3a and 3b (Ser640 and Ser644) in the control of rabbit muscle glycogen synthase. J. Biol. Chem. 270: 12491–12497, 1995.
 334. Skurat, A. V., and P. J. Roach. Regulation of glycogen biosynthesis. In: Diabetes Mellitus: A Fundamental and Clinical Text, edited by D. Le Roith, J. E. Olefsky, and S. Taylor. Philadelphia: Lippincott, 1995, p. 213–222.
 335. Skurat, A. V., Y. Wang, and P. J. Roach. Rabbit skeletal muscle glycogen synthase expressed in COS cells. Identification of regulatory phosphorylation sites. J. Biol. Chem. 269: 25534–25542, 1994.
 336. Smith, R. L., and J. C. Lawrence, Jr.. Insulin action in denervated skeletal muscle. Evidence that the reduced stimulation of glycogen synthesis does not involve decreased insulin binding. J. Biol. Chem. 260: 273–278, 1985.
 337. Smythe, C., F. B. Caudwell, M. Ferguson, and P. Cohen. Isolation and structural analysis of a peptide containing the novel tyrosyl‐glucose linkage in glycogenin. EMBO J. 7: 2681–2686, 1988.
 338. Smythe, C., and P. Cohen. The discovery of glycogenin and the priming mechanism for glycogen biogenesis. Eur. J. Biochem. 200: 625–631, 1991.
 339. Smythe, C., C. Villar‐Palasi, and P. Cohen. Structural and functional studies on rabbit liver glycogenin. Eur. J. Biochem. 183: 205–209, 1989.
 340. Smythe, C., P. Watt, and P. Cohen. Further studies on the role of glycogenin in glycogen biosynthesis. Eur. J. Biochem. 189: 199–204, 1990.
 341. Stalmans, W.. The role of the liver in the homeostasis of blood glucose. Curr. Top. Cell. Regul. 11: 51–97, 1976.
 342. Stalmans, W., M. Bollen, and L. Mvumbi. Control of glycogen synthesis in health and disease. Diabetes Metab. Rev. 3: 127–61, 1987.
 343. Stalmans, W., J. Cadefau, S. Wera, and M. Bollen. New insight into the regulation of liver glycogen metabolism by glucose. Biochem. Soc. Trans. 25: 19–25, 1997.
 344. Stalmans, W., H. De Wulf, L. Hue, and H. G. Hers. The sequential inactivation of glycogen phosphorylase and activation of glycogen synthetase in liver after the administration of glucose to mice and rats. The mechanism of the hepatic threshold to glucose. Eur. J. Biochem. 41: 117–134, 1974.
 345. Stetten, M. R., and H. M. Katzen. Degradation of glycogen by alkali. J. Am. Coll. Surg. 83: 2912–2918, 1961.
 346. Stokoe, D., L. R. Stephens, T. Copeland, P. R. Gaffney, C. B. Reese, G. F. Painter, A. B. Holmes, F. McCormick, and P. T. Hawkins. Dual role of phosphatidylinositol‐3,4,5‐trisphosphate in the activation of protein kinase B [see comments]. Science 277: 567–570, 1997.
 347. Stralfors, P.. Insulin second messengers. Bioessays 19: 327–335, 1997.
 348. Stralfors, P., A. Hiraga, and P. Cohen. The protein phosphatases involved in cellular regulation. Purification and characterisation of the glycogen‐bound form of protein phosphatase‐1 from rabbit skeletal muscle. Eur. J. Biochem. 149: 295–303, 1985.
 349. Stuart, J. S., D. L. Frederick, C. M. Varner, and K. Tatchell. The mutant type 1 protein phosphatase encoded by glc7–1 from Saccharomyces cerevisiae fails to interact productively with the GAC1‐encoded regulatory subunit. Mol. Cell. Biol. 14: 896–905, 1994.
 350. Sturgill, T. W., L. B. Ray, E. Erikson, and J. L. Maller. Insulin‐stimulated MAP‐2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature 334: 715–718, 1988.
 351. Sun, X. J., L. M. Wang, Y. Zhang, L. Yenush, M. G. Myers, Jr., E. Glasheen, W. S. Lane, J. H. Pierce, and M. F. White. Role of IRS‐2 in insulin and cytokine signalling. Nature 377: 173–177, 1995.
 352. Sutherland, C., D. G. Campbell, and P. Cohen. Identification of insulin‐stimulated protein kinase‐1 as the rabbit equivalent of rskmo‐2. Identification of two threonines phosphorylated during activation by mitogen‐activated protein kinase. Eur. J. Biochem. 212: 581–588, 1993.
 353. Sutherland, C., I. A. Leighton, and P. Cohen. Inactivation of glycogen synthase kinase‐3 beta by phosphorylation: new kinase connections in insulin and growth‐factor signalling. Biochem. J. 296: 15–19, 1993.
 354. Sutherland, E. W., and G. A. Robison. The role of cyclic AMP in the control of carbohydrate metabolism. Diabetes 18: 797–819, 1969.
 355. Tagaya, M., K. Nakano, and T. Fukui. A new affinity labeling reagent for the active site of glycogen synthase. Uridine diphospho‐pyridoxal. J. Biol. Chem. 260: 6670–6676, 1985.
 356. Takeda, Y., H. B. Brewer, Jr., and J. Larner. Structural studies on rabbit muscle glycogen synthase. I. Subunit composition. J. Biol. Chem. 250: 8943–8950, 1975.
 357. Tamemoto, H., T. Kadowaki, K. Tobe, et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate‐1 [see comments]. Nature 372: 182–186, 1994.
 358. Tan, A. W., and F. Q. Nuttall. Regulation of synthase phosphatase and phosphorylase phosphatase in rat liver. Biochim. Biophys. Acta 445: 118–130, 1976.
 359. Tang, P. M., J. A. Bondor, K. M. Swiderek, and A. A. De Paoli‐Roach. Molecular cloning and expression of the regulatory (RG1) subunit of the glycogen‐associated protein phosphatase. J. Biol. Chem. 266: 15782–15789, 1991.
 360. Tanti, J. F., T. Gremeaux, S. Grillo, V. Calleja, A. Klippel, L. T. Williams, E. Van Obberghen, and Y. Le Marchand‐Brustel. Overexpression of a constitutively active form of phosphatidylinositol 3‐kinase is sufficient to promote Glut 4 translocation in adipocytes. J. Biol. Chem. 271: 25227–25232, 1996.
 361. Tanti, J. F., S. Grillo, T. Gremeaux, P. J. Coffer, E. Van Obberghen, and Y. Le Marchand‐Brustel. Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes. Endocrinology 138: 2005–2010, 1997.
 362. Tappy, L., P. Dussoix, P. Iynedjian, S. Henry, P. Schneiter, G. Zahnd, E. Jequier, and J. Philippe. Abnormal regulation of hepatic glucose output in maturity‐onset diabetes of the young caused by a specific mutation of the glucokinase gene. Diabetes 46: 204–208, 1997.
 363. Taylor, C., A. J. Cox, J. C. Kemohan, and P. Cohen. Debranching enzyme from rabbit skeletal muscle. Purification, properties and physiological role. Eur. J. Biochem. 51: 105–115, 1975.
 364. Thakkar, J. K., M. S. Raju, A. S. Kennington, B. Foil, and J. F. Caro. [3H]Myoinositol incorporation into phospholipids in liver microsomes from humans with and without type II diabetes. The lack of synthesis of glycosylphosphatidylinositol, precursor of the insulin mediator inositol phosphate glycan. J. Biol. Chem. 265: 5475–5481, 1990.
 365. Thon, V. J., M. Khalil, and J. F. Cannon. Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast. J. Biol. Chem. 268: 7509–7513, 1993.
 366. Thorens, B., J. S. Flier, H. F. Lodish, and B. B. Kahn. Differential regulation of two glucose transporters in rat liver by fasting and refeeding and by diabetes and insulin treatment. Diabetes 39: 712–719, 1990.
 367. Titani, K., A. Koide, L. H. Ericsson, S. Kumar, J. Hermann, R. D. Wade, K. A. Walsh, H. Neurath, and E. H. Fischer. Sequence of the carboxyl‐terminal 492 residues of rabbit muscle glycogen phosphorylase including the pyridoxal 5; pr'‐phosphate binding site. Biochemistry 17: 5680–5693, 1978.
 368. Toth, B., M. Bollen, and W. Stalmans. Acute regulation of hepatic protein phosphatases by glucagon, insulin, and glucose. J. Biol. Chem. 263: 14061–14066, 1988.
 369. Toyoda, Y., I. Miwa, M. Kamiya, S. Ogiso, T. Nonogaki, S. Aoki, and J. Okuda. Tissue and subcellular distribution of glucokinase in rat liver and their changes during fasting‐refeeding. Histochem. Cell. Biol. 103: 31–38, 1995.
 370. Tsai, L. H., I. Delalle, V. S. Caviness, Jr., T. Chae, and E. Harlow. p35 is a neural‐specific regulatory subunit of cyclin‐dependent kinase 5. Nature 371: 419–423, 1994.
 371. Valera, A., and F. Bosch. Glucokinase expression in rat hepatoma cells induces glucose uptake and is rate limiting in glucose utilization. Eur. J. Biochem. 222: 533–539, 1994.
 372. van de Werve, G., and B. Jeanrenaud. Liver glycogen metabolism: an overview. Diabetes Metab. Rev. 3: 47–78, 1987.
 373. Van Schaftingen, E.. Short‐term regulation of glucokinase. Diabetologia 37: S43–S47, 1994.
 374. van Schaftingen, E., M. Veiga‐da‐Cunha, and L. Niculescu. The regulatory protein of glucokinase. Biochem. Soc. Trans. 25: 136–40, 1997.
 375. Velho, G., K. F. Petersen, G. Perseghin, J. H. Hwang, D. L. Rothman, M. E. Pueyo, G. W. Cline, P. Froguel, and G. I. Shulman. Impaired hepatic glycogen synthesis in glucokinase‐deficient (MODY‐2) subjects. J. Clin. Invest. 98: 1755–1761, 1996.
 376. Villar‐Palasi, C.. Inhibition by glucose 6‐phosphate of cyclic AMP‐dependent protein kinase phosphorylation of glycogen synthase. Biochim. Biophys. Acta 1207: 88–92, 1994.
 377. Villar‐Palasi, C.. Substrate specific activation by glucose 6‐phosphate of the dephosphorylation of muscle glycogen synthase. Biochim. Biophys. Acta 1095: 261–267, 1991.
 378. Villar‐Palasi, C., and J. J. Guinovart. The role of glucose 6‐phosphate in the control of glycogen synthase. FASEB J. 11: 544–558, 1997.
 379. Villar‐Palasi, C., and J. Larner. Insulin‐mediated effect on the activity of UDPG‐glycogen transglucosylase of muscle. Biochim. Biophys. Acta 39: 171–173, 1960.
 380. Viskupic, E., Y. Cao, W. Zhang, C. Cheng, A. A. De Paoli‐Roach, and P. J. Roach. Rabbit skeletal muscle glycogenin. Molecular cloning and production of fully functional protein in Escherichia coli. J. Biol. Chem. 267: 25759–25763, 1992.
 381. Walkenbach, R. J., R. Hazen, and J. Larner. Reversible inhibition of cyclic AMP‐dependent protein kinase by insulin. Mol. Cell. Biochem. 19: 31–41, 1978.
 382. Wang, Y., M. Camici, F. T. Lee, Z. Ahmad, A. A. De Paoli‐Roach, and P. J. Roach. Multiple phosphorylation sites of rat liver glycogen synthase. Biochim. Biophys. Acta 888: 225–236, 1986.
 383. Wawrzynczak, E. J., and R. N. Perham. Isolation and nucleotide sequence of a cDNA encoding human calmodulin. Biochem. Int. 9: 177–85, 1984.
 384. Welsh, G. I., and C. G. Proud. Glycogen synthase kinase‐3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor e1F‐2B. Biochem. J. 294: 625–629, 1993.
 385. White, M. F., and C. R. Kahn. The insulin signaling system. J. Biol. Chem. 269: 1–4, 1994.
 386. White, R. C., and T. E. Nelson. Analytical gel chromatography of rabbit muscle amylo‐1,6‐glucosidase/4‐alpha‐glucanotransferase under denaturing and non‐denaturing conditions. Biochim. Biophys. Acta 400: 154–61, 1975.
 387. Wiese, R. J., C. C. Mastick, D. F. Lazar, and A. R. Saltiel. Activation of mitogen‐activated protein kinase and phosphatidylinositol 3′‐kinase is not sufficient for the hormonal stimulation of glucose uptake, lipogenesis, or glycogen synthesis in 3T3‐L1 adipocytes. J. Biol. Chem. 270: 3442–6344, 1995.
 388. Withers, D. J., D. M. Ouwens, B. T. Nave, G. C. M., Van Der Zon, C. M. Alarcon, M. E. Cardenas, J. Heitman, J. A. Maassen, and P. R. Shepherd. Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin‐responsive cells. Biochem. Biophys. Res. Commun. 241: 704–709, 1997.
 389. Woodgett, J. R.. Molecular cloning and expression of glycogen synthase kinase‐3/factor A. EMBO J. 9: 2431–2438, 1990.
 390. Xu, R. M., G. Carmel, R. M. Sweet, J. Kuret, and X. Cheng. Crystal structure of casein kinase‐1, a phosphate‐directed protein kinase. EMBO J. 14: 1015–1023, 1995.
 391. Yamamoto‐Honda, R., K. Tobe, Y. Kaburagi, et al. Upstream mechanisms of glycogen synthase activation by insulin and insulin‐like growth factor‐I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras. J. Biol. Chem. 270: 2729–2734, 1995.
 392. Yang, B. Z., J. H. Ding, J. J. Enghild, Y. Bao, and Y. T. Chen. Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen debranching enzyme. J. Biol. Chem. 267: 9294–9299, 1992.
 393. Yeaman, S. J., and P. Cohen. The hormonal control of activity of skeletal muscle phosphorylase kinase. Phosphorylation of the enzyme at two sites in vivo in response to adrenalin. Eur. J. Biochem. 51: 93–104, 1995.
 394. Yeh, J. I., E. A. Gulve, L. Rameh, and M. J. Birnbaum. The effects of wortmannin on rat skeletal muscle. Dissociation of signaling pathways for insulin‐and contraction‐activated hexose transport. J. Biol. Chem. 270: 2107–2111, 1995.
 395. Yonezawa, K., H. Ueda, K. Hara, et al. Insulin‐dependent formation of a complex containing an 85‐kDa subunit of phosphatidylinositol 3‐kinase and tyrosine‐phosphorylated insulin receptor substrate 1. J. Biol. Chem. 267: 25958–25965, 1992.
 396. Zander, N. F., H. E. Meyer, E. Hoffmann‐Posorske, J. W. Crabb, L. M. Heilmeyer, Jr., and M. W. Kilimann. cDNA cloning and complete primary structure of skeletal muscle phosphorylase kinase (alpha subunit). Proc. Natl. Acad. Sci. U.S.A. 85: 2929–2933, 1988.
 397. Zhang, J. N., J. Hiken, A. E. Davis, and J. C. Lawrence, Jr.. Insulin stimulates dephosphorylation of phosphorylase in rat epitrochlearis muscles. J. Biol. Chem. 264: 17513–17523, 1989.
 398. Zhang, W., A. A. De Paoli‐Roach, and P. J. Roach. Mechanisms of multisite phosphorylation and inactivation of rabbit muscle glycogen synthase. Arch. Biochem. Biophys. 304: 219–225, 1993.
 399. Zhang, W. M., M. F. Browner, R. J. Fletterick, A. A. De Paoli‐Roach, and P. J. Roach. Primary structure of rabbit skeletal muscle glycogen synthase deduced from cDNA clones. FASEB J. 3: 2532–2536, 1989.
 400. Zhou, L., H. Chen, C. H. Lin, L.‐N. Cong, M. A. McGibbon, S. Sciacchitano, M. A. Lesniak, M. J. Quon, and S. I. Taylor. Insulin receptor substrate‐2 (IRS‐2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells. J. Biol. Chem. 272: 29829–29833, 1997.
 401. Zimmermann, H. P., V. Granzow, and C. Granzow. Nuclear glycogen synthesis in Ehrlich ascites cells. J. Ultrastruct. Res. 54: 115–23, 1976.
 402. Zorzano, A., L. Sevilla, E. Tomas, A. Guma, M. Palacin, and Y. Fischer. GLUT4 trafficking in cardiac and skeletal muscle: isolation of distinct intracellular GLUT4‐containing vesicle population. Biochem. Soc. Trans. 25: 968–974, 1997.

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Article Title: Regulation of Glycogen Metabolism
 

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Peter J. Roach, Alexander V. Skurat, Robert A. Harris. Regulation of Glycogen Metabolism. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 609-647. First published in print 2001. doi: 10.1002/cphy.cp070219