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Gut Glucagon

Dominique Bataille

10.1002/cphy.cp060220

Source: Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Gut Glucagon‐Related Peptides: Early Studies
2 Isolation of Glicentin (Proglucagon) and Oxyntomodulin (Glucagon‐37)
2.1 Isolation of Glicentin (Proglucagon)
2.2 Isolation of Oxyntomodulin (Glucagon‐37)
2.3 Relationship With Other Peptides
3 Structure of Preproglucagon Gene
4 Biosynthesis of Glucagon‐ and Gut Glucagon‐Containing Peptides
5 Distribution of Oxyntomodulin and Glicentin
6 Biological Activities of Oxyntomodulin and Glicentin
6.1 Properties of Glucagon
6.2 Interaction of Glicentin and Oxyntomodulin With Glucagon Targets
6.3 Tissue Specificity of Oxyntomodulin
7 Circulating Forms
8 Possible Roles in Physiology and Pathology
9 New Perspective: Other Preproglucagon Fragments
9.1 Proglucagon 51–61 (Glucagon 19–29)
9.2 Proglucagon 51–69 (Oxyntomodulin 19–37)
10 Conclusions
Figure 1. Figure 1.

Primary structure of mammalian glucagon displayed with 3‐letter code for amino acids (top) and 1‐letter code (bottom). ‐, Acidic residues; +, basic residues; arrows, sites of cleavage by trypsin or trypsinlike enzymes; asterisks, tyrosine residues that may be labeled with radioactive iodine.
Figure 2. Figure 2.

The two immunological determinants (epitopes) of glucagon. Top: “N‐term” (NH2‐terminal), epitope 11–16; “C‐term” (COOH‐terminal), epitope 24–29. Bottom: in glucagon‐containing peptides extended at COOH‐terminal end (such as glicentin or oxyntomodulin), NH2‐terminal epitope is as accessible as in glucagon (cross‐reaction with NH2‐terminal antisera = 100%), whereas COOH‐terminal epitope is masked

cross‐reaction with COOH‐terminal antisera ˜1%
Figure 3. Figure 3.

Variations in plasma glucose, insulin (IRI), gut glucagon‐like immunoreactivity (GLI), and pancreatic GLI (pancreatic‐type glucagon) in normal human subjects during oral glucose‐tolerance test (OGTT).

From Heding 66
Figure 4. Figure 4.

Primary structure of porcine glicentin (proglucagon) and oxyntomodulin (glucagon‐37). Arrows, sites of cleavage for processing enzymes that yield glicentin‐related pancreatic peptide (GRPP), glucagon, and COOH‐terminal hexapeptide in pancreas and oxyntomodulin in intestine. Glucagon and oxyntomodulin have a free NH2‐terminal histidine, whereas this residue is masked by GRPP in glicentin. Structure of oxyntomodulin is compared with that of other glucagon‐related peptides coded by other genes [secretin, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastric inhibitory polypeptide (GIP), and growth hormone‐releasing factor (GRF)] or by same gene [glucagon‐like peptides 1 and 2 (GLP‐1 and GLP‐2)]. All peptides are of porcine origin except GLP‐1, GLP‐2, and GRF, which are of human origin. Amino acids are represented with single‐letter code 84): A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, He; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gin; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; Y, Tyr.
Figure 5. Figure 5.

Comparative structures of glucagon‐containing peptides in mammalian species (pig, cattle, hamster, human, rat). Amino acids are represented with single‐letter code 84): A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gin; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; Y, Tyr.
Figure 6. Figure 6.

Structure of preproglucagon gene. Residues −20 to 0 correspond to signal peptide, and 1 to 160 to preproglucagon, which is further processed to yield the different fragments. GRPP, glicentin‐related pancreatic peptide; OXM, oxyntomodulin; GLU, glucagon; 6, COOH‐terminal hexapeptide; GLP‐1 and GLP‐2, glucagon‐like peptides 1 and 2; N, NH2‐terminal epitope of glucagon; C, COOH‐terminal epitope of glucagon. Proposed processing in pancreas and intestine comes from available data.
Figure 7. Figure 7.

Gel‐filtration profiles of extracts of porcine pancreas (B, D, F, H) and of purified glicentin (A, C, E, G) as measured by 6–15 immunoreactive (A, B) and 19–29 immunoreactive antisera to glucagon and 15–30 immunoreactive antisera to glucagon and 15–30 immunoreactive CE, F) and 61–69 immunoreactive (G, H) antisera to glicentin, and plotted against the distribution coefficient (Kd). According to the characteristics of the known peptides, the following peptides are eluted (left to right). B: glicentin, oxyntomodulin, glucagon; D: glucagon; F: glicentin, GRPP; H: glicentin, oxyntomodulin, unknown (shoulder), hexapeptide. Note that glicentin and oxyntomodulin are present in equal amounts (B and H).

Adapted from Sheikh et al. 168
Figure 8. Figure 8.

Gel‐filtration profiles of immunoreactive hexapeptide (A) and immunoreactive pancreatic glucagon (B) in crude extracts of rat pancreas. It may be seen in A, using a radioimmunoassay recognizing molecules bearing COOH‐terminal epitope of glicentin, that there is no detectable peak at glicentin level and that there is a peak eluted between glicentin and hexapeptide glicentin (64–69) peak, which corresponds to oxyntomodulin. This peak represents 20% of total immunoreactivity eluted (cf. Fig. 10, left). Peak in B is glucagon. Note same amount of glucagon (B) and hexapeptide (A).

From Yanaihara et al. 212
Figure 9. Figure 9.

Presence of the different glucagon‐containing peptides in human pancreatic (top) and jejunal (bottom) extracts. Extracts were separated by reverse‐phase high‐performance liquid chromatography followed by NH2‐terminal radioimmunoassay. GLC, glicentin (glucagon‐69); OXM, oxyntomodulin (glucagon‐37); GLU, glucagon (glucagon‐29).

Data from Blache et al. 22a
Figure 10. Figure 10.

Separation of crude extracts 9,131,133) of rat pancreas, stomach, and ileum by high‐performance liquid chromatography followed by radioreceptor assay of glucagon in liver membranes. In this assay only glucagon (GLU) and oxyntomodulin (OXM) are recognized. Results for oxyntomodulin were corrected for the decreased affinity of the peptide as compared with glucagon.
Figure 11. Figure 11.

Comparison of biological activities of glucagon (GLU) and oxyntomodulin (OXM). A: binding of 125I‐labeled glucagon to rat liver membranes. B: stimulation of adenylate cyclase in same membranes. C: stimulation of insulin release from perfused rat pancreas. D: binding of 125I‐labeled oxyntomodulin to rat gastric oxyntic glands. E: stimulation of rat gastric oxyntic gland cAMP. F: inhibition of pentagastrin‐stimulated gastric acid secretion in anesthetized rat. Data are expressed as percentage of maximal effect attainable (A, B, D, E), in ng/min (C), and as percentage of total acid secreted (F).

A, B from Bataille et al. 17); C from Jarrousse et al. 87); D from Depigny et al. 42); E from Bataille et al. 12); F from Dubrasquet et al. 47
Figure 12. Figure 12.

Pharmacological characteristics of binding site for oxyntomodulin (glucagon‐37) present in rat oxyntic glands. High‐performance liquid chromatography purified monoiodinated oxyntomodulin and intact fundic (oxyntic) glands from rat gastric mucosa were used. G‐37, oxyntomodulin (glucagon‐37); G‐29, pancreatic glucagon; g, gastrin; pg, pentagastrin; h, histamine; c, carbachol.

Adapted from Depigny et al. 42
Figure 13. Figure 13.

Inhibitory effect of oxyntomodulin (G‐37) and its COOH‐terminal octapeptide on pentagastrin‐stimulated gastric acid output in the conscious rat equipped with a chronic gastric fistula. Peptides were bolus‐injected on a plateau of secretion obtained with continuous perfusion of pentagastrin (0.5 μg·kg−1·h−1).

Adapted from Jarrousse et al. 86
Figure 14. Figure 14.

Inhibitory effect of oxyntomodulin (OXM) and the COOH‐terminal octapeptide of OXM (KAs) on pentagastrin‐induced gastric acid output in conscious rat equipped with chronic gastric fistula. Data are presented as inhibition, expressed as percentage of pentagastrin effect. Peptides were bolus‐injected on plateau of secretion obtained with perfusion of pentagastrin (0.5 μg·kg−1·h−1).

Adapted from Jarrousse et al. 86
Figure 15. Figure 15.

Concentrations of glicentin (GLC), oxyntomodulin (OXM), and glucagon (GLU) in plasma of fasted and fed rats. Data expressed in pM were obtained by separation of different peptides with high‐performance liquid chromatography followed by radioimmunoassay.

Adapted from Kervran et al. 92
Figure 16. Figure 16.

Peptides shown to exist (shaded) or possibly produced (nonshaded) from first 69 amino acids of preproglucagon by processing at dibasic sites Lys‐Arg (KR) or Arg‐Arg (RR). 6 and 8, COOH‐terminal hexa‐ and octapeptides of oxyntomodulin or glicentin. 1–12, 19–29, and 19–37, NH2‐ and COOH‐terminal fragments of glucagon or oxyntomodulin. GRPP, glicentin‐related pancreatic peptide.
Figure 17. Figure 17.

Modes of action of glucagon on liver metabolism. Entire molecule (GLU) acts through receptor R2, coupled via a GTP‐binding protein (G) to adenylate cyclase (Ac) and through receptor R1, coupled via a GTP‐binding protein (G) to phospholipase C (Pc), which produces inositol trisphosphate (IP3), leading to a release of calcium from intracellular stores (endoplasmic reticulum). After glucagon cleavage at arginine 17–18 site, COOH‐terminal undecapeptide (AT11) acts through a GTP‐binding protein (G) on calcium ATPase, which controls calcium output from cell.


Figure 1.

Primary structure of mammalian glucagon displayed with 3‐letter code for amino acids (top) and 1‐letter code (bottom). ‐, Acidic residues; +, basic residues; arrows, sites of cleavage by trypsin or trypsinlike enzymes; asterisks, tyrosine residues that may be labeled with radioactive iodine.



Figure 2.

The two immunological determinants (epitopes) of glucagon. Top: “N‐term” (NH2‐terminal), epitope 11–16; “C‐term” (COOH‐terminal), epitope 24–29. Bottom: in glucagon‐containing peptides extended at COOH‐terminal end (such as glicentin or oxyntomodulin), NH2‐terminal epitope is as accessible as in glucagon (cross‐reaction with NH2‐terminal antisera = 100%), whereas COOH‐terminal epitope is masked

cross‐reaction with COOH‐terminal antisera ˜1%


Figure 3.

Variations in plasma glucose, insulin (IRI), gut glucagon‐like immunoreactivity (GLI), and pancreatic GLI (pancreatic‐type glucagon) in normal human subjects during oral glucose‐tolerance test (OGTT).

From Heding 66


Figure 4.

Primary structure of porcine glicentin (proglucagon) and oxyntomodulin (glucagon‐37). Arrows, sites of cleavage for processing enzymes that yield glicentin‐related pancreatic peptide (GRPP), glucagon, and COOH‐terminal hexapeptide in pancreas and oxyntomodulin in intestine. Glucagon and oxyntomodulin have a free NH2‐terminal histidine, whereas this residue is masked by GRPP in glicentin. Structure of oxyntomodulin is compared with that of other glucagon‐related peptides coded by other genes [secretin, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastric inhibitory polypeptide (GIP), and growth hormone‐releasing factor (GRF)] or by same gene [glucagon‐like peptides 1 and 2 (GLP‐1 and GLP‐2)]. All peptides are of porcine origin except GLP‐1, GLP‐2, and GRF, which are of human origin. Amino acids are represented with single‐letter code 84): A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, He; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gin; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; Y, Tyr.



Figure 5.

Comparative structures of glucagon‐containing peptides in mammalian species (pig, cattle, hamster, human, rat). Amino acids are represented with single‐letter code 84): A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gin; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; Y, Tyr.



Figure 6.

Structure of preproglucagon gene. Residues −20 to 0 correspond to signal peptide, and 1 to 160 to preproglucagon, which is further processed to yield the different fragments. GRPP, glicentin‐related pancreatic peptide; OXM, oxyntomodulin; GLU, glucagon; 6, COOH‐terminal hexapeptide; GLP‐1 and GLP‐2, glucagon‐like peptides 1 and 2; N, NH2‐terminal epitope of glucagon; C, COOH‐terminal epitope of glucagon. Proposed processing in pancreas and intestine comes from available data.



Figure 7.

Gel‐filtration profiles of extracts of porcine pancreas (B, D, F, H) and of purified glicentin (A, C, E, G) as measured by 6–15 immunoreactive (A, B) and 19–29 immunoreactive antisera to glucagon and 15–30 immunoreactive antisera to glucagon and 15–30 immunoreactive CE, F) and 61–69 immunoreactive (G, H) antisera to glicentin, and plotted against the distribution coefficient (Kd). According to the characteristics of the known peptides, the following peptides are eluted (left to right). B: glicentin, oxyntomodulin, glucagon; D: glucagon; F: glicentin, GRPP; H: glicentin, oxyntomodulin, unknown (shoulder), hexapeptide. Note that glicentin and oxyntomodulin are present in equal amounts (B and H).

Adapted from Sheikh et al. 168


Figure 8.

Gel‐filtration profiles of immunoreactive hexapeptide (A) and immunoreactive pancreatic glucagon (B) in crude extracts of rat pancreas. It may be seen in A, using a radioimmunoassay recognizing molecules bearing COOH‐terminal epitope of glicentin, that there is no detectable peak at glicentin level and that there is a peak eluted between glicentin and hexapeptide glicentin (64–69) peak, which corresponds to oxyntomodulin. This peak represents 20% of total immunoreactivity eluted (cf. Fig. 10, left). Peak in B is glucagon. Note same amount of glucagon (B) and hexapeptide (A).

From Yanaihara et al. 212


Figure 9.

Presence of the different glucagon‐containing peptides in human pancreatic (top) and jejunal (bottom) extracts. Extracts were separated by reverse‐phase high‐performance liquid chromatography followed by NH2‐terminal radioimmunoassay. GLC, glicentin (glucagon‐69); OXM, oxyntomodulin (glucagon‐37); GLU, glucagon (glucagon‐29).

Data from Blache et al. 22a


Figure 10.

Separation of crude extracts 9,131,133) of rat pancreas, stomach, and ileum by high‐performance liquid chromatography followed by radioreceptor assay of glucagon in liver membranes. In this assay only glucagon (GLU) and oxyntomodulin (OXM) are recognized. Results for oxyntomodulin were corrected for the decreased affinity of the peptide as compared with glucagon.



Figure 11.

Comparison of biological activities of glucagon (GLU) and oxyntomodulin (OXM). A: binding of 125I‐labeled glucagon to rat liver membranes. B: stimulation of adenylate cyclase in same membranes. C: stimulation of insulin release from perfused rat pancreas. D: binding of 125I‐labeled oxyntomodulin to rat gastric oxyntic glands. E: stimulation of rat gastric oxyntic gland cAMP. F: inhibition of pentagastrin‐stimulated gastric acid secretion in anesthetized rat. Data are expressed as percentage of maximal effect attainable (A, B, D, E), in ng/min (C), and as percentage of total acid secreted (F).

A, B from Bataille et al. 17); C from Jarrousse et al. 87); D from Depigny et al. 42); E from Bataille et al. 12); F from Dubrasquet et al. 47


Figure 12.

Pharmacological characteristics of binding site for oxyntomodulin (glucagon‐37) present in rat oxyntic glands. High‐performance liquid chromatography purified monoiodinated oxyntomodulin and intact fundic (oxyntic) glands from rat gastric mucosa were used. G‐37, oxyntomodulin (glucagon‐37); G‐29, pancreatic glucagon; g, gastrin; pg, pentagastrin; h, histamine; c, carbachol.

Adapted from Depigny et al. 42


Figure 13.

Inhibitory effect of oxyntomodulin (G‐37) and its COOH‐terminal octapeptide on pentagastrin‐stimulated gastric acid output in the conscious rat equipped with a chronic gastric fistula. Peptides were bolus‐injected on a plateau of secretion obtained with continuous perfusion of pentagastrin (0.5 μg·kg−1·h−1).

Adapted from Jarrousse et al. 86


Figure 14.

Inhibitory effect of oxyntomodulin (OXM) and the COOH‐terminal octapeptide of OXM (KAs) on pentagastrin‐induced gastric acid output in conscious rat equipped with chronic gastric fistula. Data are presented as inhibition, expressed as percentage of pentagastrin effect. Peptides were bolus‐injected on plateau of secretion obtained with perfusion of pentagastrin (0.5 μg·kg−1·h−1).

Adapted from Jarrousse et al. 86


Figure 15.

Concentrations of glicentin (GLC), oxyntomodulin (OXM), and glucagon (GLU) in plasma of fasted and fed rats. Data expressed in pM were obtained by separation of different peptides with high‐performance liquid chromatography followed by radioimmunoassay.

Adapted from Kervran et al. 92


Figure 16.

Peptides shown to exist (shaded) or possibly produced (nonshaded) from first 69 amino acids of preproglucagon by processing at dibasic sites Lys‐Arg (KR) or Arg‐Arg (RR). 6 and 8, COOH‐terminal hexa‐ and octapeptides of oxyntomodulin or glicentin. 1–12, 19–29, and 19–37, NH2‐ and COOH‐terminal fragments of glucagon or oxyntomodulin. GRPP, glicentin‐related pancreatic peptide.



Figure 17.

Modes of action of glucagon on liver metabolism. Entire molecule (GLU) acts through receptor R2, coupled via a GTP‐binding protein (G) to adenylate cyclase (Ac) and through receptor R1, coupled via a GTP‐binding protein (G) to phospholipase C (Pc), which produces inositol trisphosphate (IP3), leading to a release of calcium from intracellular stores (endoplasmic reticulum). After glucagon cleavage at arginine 17–18 site, COOH‐terminal undecapeptide (AT11) acts through a GTP‐binding protein (G) on calcium ATPase, which controls calcium output from cell.

References
 1. Ahren, B., and I. Lundqvist. Effects of glicentin on insulin secretion. Horm. Metab. Res. 12: 582–586, 1980.
 2. Andersson, S. Gastric and duodenal mechanisms inhibiting gastric secretion of acid. In: Handbook of Physiology. Alimentary Canal. Secretion, edited by C. F. Code. Washington, DC: Am. Physiol. Soc., 1967, sect. 6, vol. I, chapt. 48, p. 865–877.
 3. Assan, R., and N. Slusher. Structure/function and structure/immunoreactivity relationships of the glucagon molecules and related synthetic peptides. Diabetes 21: 843–855, 1972.
 4. Audousset‐Puech, M. P., C., Jarrousse, M. Dubrasquet, A. Aumelas, B. Castro, D. Bataille, and J. Martinez. Synthesis of the C‐terminal octapeptide of pig oxyntomodulin. Lys‐Arg‐Asn‐Lys‐Asn‐Asn‐Ile‐Ala: a potent inhibitor of pentagastrin‐induced acid secretion. J. Med. Chan. 28: 1529–1533, 1985.
 5. Baetens, D., C., Rufener, B. C. Srikant, R. Dobbs, R. Unger, and L. Orci. Identification of glucagon producing cells (A cells) in dog gastric mucosa. J. Cell Biol. 69: 455–464, 1976.
 6. Baldissera, F. G. A., and J. J. Holst. Glucagon‐related peptides in the human gastrointestinal mucosa. Diabetologia 26: 223–228, 1984.
 7. Banting, F. G., and C. H. Best. The internal secretion of the pancreas. J. Lab. Clin. Med. 7: 251–266, 1922.
 8. Bataille, D., J., Besson, C. Gespach, and G. Rosselin. High performance liquid chromatography of hormonal peptides. Use of trifluoroacetic acid/diethylamine for their separation. In: Hormone Receptors in Digestion and Nutrition, edited by G. Rosselin, P. Fromageot, and S. Bonfils. Amsterdam: Elsevier/North‐Holland, 1979, p. 79–87.
 9. Bataille, D., P., Blache, F. Mercier, C. Jarrousse, A. Kervran, M. Dufour, P. Mangeat, M. Dubrasquet, A. Mallat, S. Lotersztajn, C. Pavoine, and F. Pecker. Glucagon and related peptides: molecular structure and biological specificity. Ann. NY Acad. Sci. 527: 168–185, 1988.
 10. Bataille, D., A. M., Coudray, M. Carlqvist, G. Rosselin, and V. Mutt. Isolation of glucagon‐37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno‐ileum. Isolation of the peptide. FEB S Lett. 146: 73–78, 1982.
 11. Bataille, D. P., P., Freychet, P. E. Kitabgi, and G. Rosselin. Gut glucagon: a common receptor site with pancreatic glucagon in liver cell plasma membranes. FEBS Lett. 30: 215–218, 1973.
 12. Bataille, D., P., Freychet, and G. Rosselin. Interactions of glucagon, gut glucagon, vasoactive intestinal polypeptide and secretin with liver and fat cell plasma membranes: binding to specific sites and stimulation of adenylate cyclase. Endocrinology 95: 713–721, 1974.
 13. Bataille, D., C., Gespach, A. M. Coudray, and G. Rosselin. “Enteroglucagon”: a specific effect on gastric glands isolated from the rat fundus. Evidence for an “oxyntomodulin” action. Biosci. Rep. 1: 151–155, 1981.
 14. Bataille, D., C., Gespach, K. Tatemoto, J. C. Marie, A. M. Coudray, G. Rosselin, and V. Mutt. Biologically active “enteroglucagon” (“oxyntomodulin”): present knowledge on its chemical structure and its biological activity. Peptides Fayetteville 2, Suppl. 2: 247–251, 1981.
 15. Bataille, D., C., Jarrousse, A. Kervran, C. Depigny, and M. Dubrasquet. The biological significance of “enteroglucagon.” Present status. Peptides Fayetteville 7, Suppl. 1: 37–42, 1986.
 16. Bataille, D., G., Rosselin, P. Freychet, and V. Mutt. Partial purification and characterization of active “enteroglucagon” from porcine jejuno‐ileum (Abstract). Diabetologia 11: 331, 1975.
 17. Bataille, D., K., Tatemoto, A. M. Coudray, G. Rosselin, and V. Mutt. ”Enteroglucagon” bioactif (oxyntomodulin): évidence pour une extension C‐terminale de la molécule de glucagon. C.R. Seances Acad. Sci. Ser. III Sci. Vie. 293: 323–328, 1981.
 18. Bataille, D., K., Tatemoto, C. Gespach, H. Jörnvall, G. Rosselin, and V. Mutt. Isolation of glucagon‐37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno‐ileum. Characterization of the peptide. FEBS Lett. 146: 79–86, 1982.
 19. Bell, G. I., R., Sanchez‐Pescador, P. J. Laybourn, and R. C. Najarian. Exon duplication and divergence in the human preproglucagon gene. Nature Lond. 304: 368–371, 1983.
 20. Bell, G. I., R. F., Santerre, and G. T. Mullenbach. Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature Lond. 302: 716–718, 1983.
 21. Biedzinski, T. M., D., Bataille, M. A. Devaux, and H. Sarles. The action of oxyntomodulin (bioactive enteroglucagon, glucagon‐37) and glucagon on pancreatic secretion in the conscious rat. Peptides Fayetteville 8: 967–972, 1987.
 22. Binger, J., J., Mirouze, G. Marchal, T. C. Pham, A. Luyckx, P. Lefebvre, and A. Orsetti. Glucagon immunoreactivity and antidiabetic action of somatostatin in the totally duodeno‐pancreatectomized and gastrectomized human. Diabetes 30: 851–856, 1981.
 23. Blache, P., A., Kervran, J. Martinez, and D. Bataille. Development of an oxyntomodulin/glicentin C‐terminal radioimmunoassay using a “thiol‐maleoyl” coupling method for preparing the immunogen. Anal. Biochem. 173: 151–159, 1988.
 24. Bloom, S. R. An enteroglucagon tumor. Gut 13: 520–523, 1972.
 25. Bloom, S. R., C. M. S., Roysten, and J. P. S. Thompson. Enteroglucagon release in the dumping syndrome. Lancet 2: 789–791, 1972.
 26. Botha, J. L., A. J., Vinik, and J. C. Brown. Gastric inhibitory polypeptide (GIP) in chronic pancreatitis. J. Clin. Endocrinol. Metabol. 42: 791–797, 1976.
 27. Bottger, I., R., Dobbs, G. R. Faloona, and R. H. Unger. The effects of triglyceride absorption upon glucagon, insulin and gut glucagon‐like immunoreactivity. J. Clin. Invest. 52: 2532–2541, 1973.
 28. Bromer, W. W., L. G., Sinn, and O. K. Behrens. The amino acid sequence of glucagon. V. Location of amide groups, acid degradation studies and summary of sequential evidence. J. Am. Chem. Soc. 79: 2807–2810, 1957.
 29. Bryant, M. G., and S. R. Bloom. Distribution of the gut hormones in the primate intestinal tract. Gut 20: 653–659, 1979.
 30. Buchan, A. M. J., and J. M. Polak. The classification of the human gastroenteropancreatic endocrine cells. Invest. Cell Pathol. 3: 51–71, 1980.
 31. Bussolati, G., C., Capella, G. Vassallo, and E. Solcia. Histochemical and ultrastructural studies on pancreatic A cells. Evidence for glucagon and non‐glucagon components of the alpha granule. Diabetologia 7: 181–188, 1971.
 32. Chisholm, D. J., F. P., Halford, M. S. Harewood, D. M. Findlay, and B. N. Gray. Nature and biological activity of “extrapancreatic glucagon”: studies in pancreatectomized cats. Metabolism 27: 261–273, 1978.
 33. Christiansen, J., A., Bech, J. Fahrenkrug, J. J. Holst, K. Lauritsen, A. J. Moody, and O. Schaffalitzky DE Mück‐Adell. Fat‐induced jejunal inhibition of gastric acid secretion and release of pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide and vasoactive intestinal polypeptide in man. Scand. J. Gastroenterol. 14: 161–166, 1979.
 34. Christiansen, J., J. J., Holst, and E. Kalaja. Inhibition of gastric acid secretion in man by exogenous and endogenous pancreatic glucagon. Gastroenterology 70: 688–692, 1976.
 35. Cohen, P. Proteolytic events in the post‐translational processing of polypeptide hormone precursors. Biochimie Paris 69: 87–89, 1987.
 36. Colony, P. C., V., Helmstaedter, A. J. Moody, J. C. Garaud, and W. G. Forssmann. Glucagon and glicentin immunoreactive cells in human colon. Cell Tissue Res. 221: 483–491, 1982.
 37. Conlon, J. M., H. F., Hansen, and T. W. Schwartz. Primary structure of glucagon and a partial sequence of oxyntomodulin (glucagon‐37) from the guinea pig. Regul. Pept. 11: 309–320, 1985.
 38. Conlon, J. M., R. F., Murphy, and K. D. Buchanan. Physicochemical and biological properties of glucagon‐like polypeptides from porcine colon. Biochim. Biophys. Acta 254: 2229–2233, 1979.
 39. Conlon, J. M., D., Rouiller, and R. H. Unger. Characterization of the glucagon‐like polypeptides released by the dog gut into the circulation. Biochem. Soc. Trans. 8: 51–52, 1980.
 40. Conlon, J. M., W. K., Samson, R. E. Dobbs, L. Orci, and R. H. Unger. Glucagon‐like polypeptides in canine brain. Diabetes 28: 700–702, 1979.
 41. Czyzyk, A., L. G., Heding, B. Malczewski, and E. Miedzinska. The effect of phenformin upon the plasma pancreatic and gut glucagon‐like immunoreactivity in diabetics. Diabetologia 11: 129–133, 1975.
 42. Dammann, H. G., H. S., Besterman, S. R. Bloom, and H. W. Schreiber. Gut‐hormone profile in totally pancreatectomized patients. Gut 22: 103–107, 1981.
 43. Depigny, C., B., Lupo, A. Kervran, and D. Bataille. Mise en évidence d'un site récepteur spécifique du glucagon‐37 (oxyntomoduline/entéroglucagon bioactif) dans les glandes oxyntiques de rat. C.R. Sceances Acad. Sci. Ser. III Sci. Vie. 299: 677–680, 1984.
 44. Depigny, C., F., Mercier, B. Lupo, and D. Bataille. Compared tissue specificity of glucagon and oxyntomodulin (glucagon‐37). Program, Regulatory Peptides, Gouvieux, May 9–11, 1985, p. 135.
 45. Desbuquois, B. The interaction of vasoactive intestinal polypeptide and secretin with liver‐cell membranes. Eur. J. Biochem. 46: 439–450, 1974.
 46. Doi, K., M., Prentki, C. Yip, W. A. Müller, B. Jeanrenaud, and M. Vranic. Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon. J. Clin. Invest. 63: 525–531, 1979.
 47. Dubrasquet, J. M., M. P., Audousset‐Puech, J. Martinez, and D. Bataille. Somatostatin enhances the inhibitory effect of oxyntomodulin and its C‐terminal octapeptide on acid secretion. Peptides Fayetteville 7, Suppl. 1: 257–259, 1986.
 48. Dubrasquet, J. M., D., Bataille, and C. Gespach. Oxyntomodulin (glucagon‐37 or bioactive enteroglucagon): a potent inhibitor of pentagastrin‐stimulated acid secretion in rats. Biosci. Rep. 2: 391–395, 1982.
 49. Ensick, J. W. Immunoassays for glucagon. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. I, p. 203–221.
 50. Epand, R. M., G., Rosselin, D. Hui Bon Hoa, T. E. Cote, and M. Laburthe. Structural requirements for glucagon receptor binding and activation of adenylate cyclase in liver. J. Biol. Chem. 255: 653–658, 1981.
 51. Farah, A. E. Glucagon and the heart. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. II, p. 553–594.
 52. Fiocca, R., C., Capella, R. Buffa, R. Fontana, E. Solcia, E. Hage, R. E. Chance, and A. J. Moody. Glucagon‐, glicentin‐ and pancreatic polypeptide‐like immunoreactivities in rectal carcinoids and related colorectal cells. Am. J. Pathol. 100: 81–92, 1980.
 53. Foa, P. P., J. S., Bajaj, AND N. L. Foa (editors), Glucagon: Its Role in Physiology and Clinical Medicine. New York: Springer‐Verlag, 1977.
 54. Frame, C. M. Regional release of glucagon‐like immunoreactivity from the intestine of the cat. Horm. Metab. Res. 9: 117–120, 1977.
 55. Garaud, J. C., R., Eloy, A. J. Moody, C. Stock, and J. F. Grenier. Glucagon‐ and glicentin‐immunoreactive cells in the human digestive tract. Cell Tissue Res. 213: 121–136, 1980.
 56. George, S. K., L. O., Uttenthal, M. Ghiglione, and S. R. Bloom. Molecular forms of glucagon‐like peptides. FEBS Lett. 192: 275–278, 1985.
 57. Ghatei, M. A., L. O., Uttenthal, M. G. Bryant, N. D. Christofides, A. J. Moody, and S. R. Bloom. Molecular forms of pancratic glucagon‐like immunoreactivity in porcine intestine and pancreas. Endocrinology 112: 917–923, 1983.
 58. Gleeson, M. H., S. R., Bloom, J. M. Polak, K. Henry, and R. H. Dowling. Endocrine tumour in kidney affecting small bowel structure, motility and absorbtive function. Gut 12: 773–782, 1971.
 59. Grimelius, L., C., Capella, R. Buffa, J. M. Polak, A. G. E. Pearse, and E. Solcia. Cytochemical and ultrastructural differentiation of enteroglucagon and pancreatic‐type glucagon cells of the gastrointestinal tract. Virchows Arch. B Cell Pathol. 20: 217–228, 1976.
 60. Guillemin, R., P. Brazeau, P. Boehlen, F. Esch, N. Ling, and W. B. Wehrenberg. Growth hormone releasing factor from a human pancreatic tumor that caused acromegaly. Science Wash. DC 218: 585–587, 1982.
 61. Gutman, R. A., G., Fink, N. Voyles, H. Selawry, J. C. Penhos, A. Lepp, and L. Recant. Specific biologic effects on intestinal glucagon‐like materials. J. Clin. Invest. 52: 1165–1175, 1973.
 62. Hatton, T. W., N., Kovacevic, M. Dutczak, and M. Vranic. Glucagon‐like immunoreactants in extracts of the rat hypothalamus. Endocrinology 111: 572–577, 1982.
 63. Hatton, T. W., C. C., Yip, and M. Vranic. Biosynthesis of glucagon (IRG 3500) in canine gastric mucosa. Diabetes 34: 38–46, 1985.
 64. Heding, L. G. Radioimmunological determination of pancreatic and gut glucagon in plasma. Diabetologia 7: 10–19, 1971.
 65. Heding, L., E. K., Frandsen, and H. Jacobsen. Glucagon. Structure‐function relationship: immunologic. Metabolism 25: 1327–1329, 1976.
 66. Heding, L. G., and G. Munkgaard‐Rasmussen. Determination of pancreatic and gut glucagon in plasma. Diabetologia 8: 408–411, 1972.
 67. Heinrich, G., P., Gros, and J. F. Habener. Glucagon gene sequence. Four of six exons encode separate functional domains of rat preproglucagon. J. Biol. Chem. 259: 14082–14087, 1984.
 68. Hicks, T., and L. A. Turnberg. Influence of glucagon on the human jejunum. Gastroenterology 67: 1114–1118, 1974.
 69. Holst, J. J. Extraction, gel filtration pattern, and receptor binding of porcine gastrointestinal glucagon‐like immunoreactivity. Diabetologia 13: 159–169, 1977.
 70. Holst, J. J. Extrapancreatic glucagons. Digestion 17: 168–190, 1978.
 71. Holst, J. J. Evidence that glicentin contains the entire sequence of glucagon. Biochem. J. 187: 337–343, 1980.
 72. Holst, J. J. Gut glucagon, enteroglucagon, gut glucagonlike immunoreactivity, glicentin—current status. Gastroenterology 84: 1602–1613, 1983.
 73. Holst, J. J., J., Christiansen, and K. Kuhl. The enteroglucagon response to intrajejunal infusion of glucose, triglycerides and sodium chloride and its relation to jejunal inhibition of gastric acid. Scand. J. Gastroenterol. 11: 297–304, 1976.
 74. Holst, J. J., T. I. A., Sorensen, A. N. Andersen, F. Stadil, B. Andersen, K. B. Lauritsen, and H. C. Klein. Plasma enteroglucagon after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio. Scand. J. Gastroenterol. 14: 205–207, 1979.
 75. Hoosein, N. M., and R. S. Gurg. Human glucagon‐like peptides 1 and 2 activate rat brain adenylate cyclase. FEBS Lett. 178: 83–86, 1984.
 76. Hoosein, N. M., and R. S. Gurg. Identification of glucagon receptors in rat brain. Proc. Natl. Acad. Sci. USA 81: 4368–4372, 1984.
 77. Horigome, K., A., Ohneda, Y. Maruhama, R. Abe, and Y. Hai. Heterogeneity of extractable gut glucagon‐like immunoreactivity (GLI) and its lipolytic activity. Horm. Metab. Res. 9: 370–374, 1977.
 78. Hornnes, S., C., Kuhl, and K. B. Lauritsen. Gastrointestinal insulinotropic hormones in normal and gestational‐diabetic pregnancy: response to oral glucose. Diabetes 30: 504–509, 1981.
 79. Ito, S., T., Iwanaga, Y. Kusumoto, N. Sudo, M. Sano, T. Suzuki, and A. Shibata. Is glucagon present in the human gastric fundus? Horm. Metab. Res. 13: 419–422, 1981.
 80. Ito, S., and S. Kobayashi. Immunohistochemical demonstration of glucagon and GLI‐containing cells in the canine gut and pancreas. Arch. Histol. Jpn. 39: 193–202, 1976.
 81. Itoh, N., K. I., Obata, N. Yanaihara, and H. Okamoto. Human prepro‐vasoactive intestinal polypeptide contains a novel PHI‐27 like peptide, PHM‐27. Nature Lond. 304: 547–549, 1983.
 82. IUPAC‐IUB Commission on Biochemical Nomenclature. Eur. J. Biochem. 246: 2827–2833, 1968.
 83. Jacobsen, H., A., Demandt, A. J. Moody, and F. Sundby. Sequence analysis of porcine gut GLI‐1. Biochim. Biophys. Acta 493: 452–459, 1977.
 84. Jarrousse, C., M. P., Audousset‐Puech, M. Dubrasquet, H. Niel, J. Martinez, and D. Bataille. Oxyntomodulin (glucagon‐37) and its C‐terminal octapeptide inhibit gastric acid secretion. FEBS Lett. 188: 81–84, 1985.
 85. Jarrousse, C., D., Bataille, and B. Jeanrenaud. A pure enteroglucagon, oxyntomodulin (glucagon‐37), stimulates insulin release in perfused rat pancreas. Endocrinology 115: 102–105, 1984.
 86. Jarrousse, C., F., Mercier, J. Martinez, and D. Bataille. Oxyntomodulin (glucagon‐37): effect of the fragment 19–37 on gastric acid secretion (Abstract). Eur. Congr. Endocrinol., 1st, Copenhagen, June, 1987, p. 65.
 87. Jarrousse, C., H., Niel, M. P. Audousset‐Puech, J. Martinez, and D. Bataille. Oxyntomodulin and its C‐terminal octapeptide inhibit liquid meal‐stimulated acid secretion. Peptides Fayetteville 7, Suppl. 1: 253–256, 1986.
 88. Jaspan, J. B., and A. H. Rubenstein. Circulating glucagon: plasma profiles and metabolism in health and disease: a review. Diabetes 26: 882–904, 1977.
 89. Jörnvall, H., M., Carlqvist, S. Kwaak, S. C. Otte, C. H. S. Mcintosh, J. C. Brown, and V. Mutt. Amino acid sequence and heterogeneity of gastric inhibitory polypeptide (GIP). FEBS Lett. 123: 205–216, 1981.
 90. Kervran, A., P., Blache, and D. Bataille. Distribution of oxyntomodulin and glucagon in the gastrointestinal tract and the plasma of the rat. Endocrinology 121: 704–713, 1987.
 91. Kervran, A., M., Dubrasquet, M.‐P. Audousset‐Puech, J. Martinez, and D. Bataille. Gastrointestinal hormones. Disappearance rate of natural and synthetic oxyntomodulin (glucagon‐37) in the plasma of the rat. Can. J. Physiol. Pharmacol. Suppl.: 153, 1986.
 92. Kervran, A., C., Jarrousse, and D. Bataille. Oxyntomodulin (G‐37) and glucagon (G‐29): distribution in the gastrointestinal tract of the rat. Diabetologia 27: 295–296, 1984.
 93. Kimball, C. P., and J. R. Murlin. Aqueous extracts of pancreas. III. Some precipitation reactions of insulin. J. Biol. Chem. 58: 337–346, 1923.
 94. Kirkegaard, P., A. J., Moody, J. J. Holst, F. B. Loud, P. S. Olsen, and J. Christiansen. Glicentin inhibits gastric acid secretion in the rat. Nature Land. 297: 156–157, 1982.
 95. Knudsen, J. B., J. J., Holst, S. Asnaes, and A. Johansen. Identification of cells with pancreatic‐type and gut‐type glucagon immunoreactivity in the human colon. Acta Pathol. Microbiol. Scand. 83: 741–743, 1975.
 96. Kock, N. G., N., Darle, and G. Dotevall. Inhibition of intestinal motility in man by glucagon given intraportally. Gastroenterology 53: 88–92, 1967.
 97. Konturek, S. J., J., Tasler, and W. Obtulovicz. Characteristics of inhibition of pancreatic secretion by glucagon. Digestion 10: 138–149, 1974.
 98. Korányi, L., F., Péterfy, J. Szabó, A. Török, M. Guóth, and G. Tamas, JR. Evidence for transformation of glucagon‐like immunoreactivity of gut into pancreatic glucagon in vivo. Diabetes 30: 792–794, 1981.
 99. Krug, E., and P. Miahle. A possible role for gut GLI: an inhibitor of lipolysis. Horm. Metab. Res. 6: 465–469, 1977.
 100. Langslow, D. R. The action of gut glucagon‐like immunoreactivity and other intestinal hormones on lipolysis in chicken adipocytes. Horm. Metab. Res. 5: 428–432, 1973.
 101. Larsson, L.‐I. Somatostatin cell processes as pathways for paracrine secretion. Science Wash. DC 205: 1393–1395, 1979.
 102. Larsson, L.‐L, J., Holst, R. Håkanson, and F. Sundler. Distribution and properties of glucagon immunoreactivity in the digestive tract of various mammals: an immunohistochemical and immunochemical study. Histochemistry 44: 281–290, 1975.
 103. Leduque, P., A. J., Moody, and P. M. Dubois. Ontogeny of immunoreactive glicentin in the human gastro‐intestinal tract and endocrine pancreas. Regul. Pept. 4: 261–274, 1982.
 104. Lefebvre, P. J. (editor), Glucagon: Handbook of Experimental Pharmacology. Heidelberg, FRG: Springer‐Verlag, 1983, vol. 66, pt. I and II.
 105. Lefebvre, P. J., and A. S. Luyckx. Extrapancreatic glucagon and its regulation. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. II, p. 205–219.
 106. Lefebvre, P. J., AND R. H. Unger (editors). Glucagon: Molecular Physiology, Clinical and Therapeutic Implications. Oxford: Pergamon, 1972.
 107. Lefebvre, P. J., R. H., Unger, I. Valverde, D. Rigopoulou, A. S. Luyckx, and A. Eisentraut. Effect of dog jejunum glucagon‐like immunoreactive material on adipose tissue metabolism. Horm. Metab. Res. 1: 143–144, 1969.
 108. Lickley, H. L. A., F. W., Kemmer, D. E. Gray, N. Kovacevic, T. W. Hatton, G. Perez, and M. Vranic. Chromatographic pattern of extrapancreatic glucagon and glucagon‐like immunoreactivity before and during stimulation by epinephrine and participation of glucagon in epinephrine‐induced hepatic glucose overproduction. Surgery St. Louis 90: 186–194, 1981.
 109. Lopez, L. C., M. L., Frazier, C.‐J. Su, A. Kuman, and G. F. Saunders. Mammalian preproglucagon contains three glucagon‐related peptides. Proc. Natl. Acad. Sci. USA 80: 5485–5489, 1983.
 110. Lopez, L. C., W.‐H., Li, M. L. Frazier, C.‐C. Luo, and G. F. Saunders. Evolution of glucagon genes. Mol. Biol. Evol. 1: 335–344, 1984.
 111. Loren, I., J., Alumets, R. Håkanson, F. Sundler, and J. Thorell. Gut‐type glucagon immunoreactivity in nerves of the rat brain. Histochemistry 61: 335–341, 1979.
 112. Lotersztajn, S., R. M., Epand, A. Mallat, and F. Pecker. Inhibition by glucagon of the calcium pump in liver plasma membranes. J. Biol. Chem. 259: 8195–8201, 1984.
 113. Lotersztajn, S., C., Pavoine, A. Mallat, D. Stengel, P. A. Insel, and F. Pecker. Cholera toxin blocks glucagon‐mediated inhibition of the liver plasma membrane (Ca2+‐Mg2+)‐ATPase. J. Biol. Chem. 262: 3114–3117, 1987.
 114. Lund, P. K., R. H., Goodman, P. C. Dee, and J. F. Habener. Pancreatic preproglucagon cDNA contains two glucagon‐related coding sequences arranged in tandem. Proc. Natl. Acad. Sci. USA 79: 345–349, 1982.
 115. Lund, P. K., R. H., Goodman, and J. Habener. Pancreatic pre‐proglucagons are encoded by two separate mRNAs. J. Biol. Chem. 256: 6515–6518, 1981.
 116. Makman, M. H., and E. W. Sutherland. Use of liver adenyl cyclase for assay of glucagon in human gastrointestinal tract and pancreas. Endocrinology 75: 127–134, 1964.
 117. Mallat, A., C., Pavoine, M. Dufour, S. Lotersztajn, D. Bataille, and F. Pecker. A glucagon fragment is responsible for the inhibition of the liver Ca2+ pump by glucagon. Nature Lond. 325: 620–622, 1987.
 118. Markussen, J., and F. Sundby. Separation and characterization of glucagon‐like immunoreactive components from gut extracts by isoelectrofocusing. In: Protides of the Biological Fluids, edited by H. Peeters. Oxford: Pergamon, 1970, p. 471–474.
 119. Matsuyama, T., and P. P. Foa. Plasma glucose, insulin, pancreatic and enteroglucagon levels in normal and depancreatized dogs. Proc. Soc. Exp. Biol. Med. 124: 97–102, 1974.
 120. Matsuyama, T., W. H., Hoffmann, J. C. Dunbar, N. L. Foa, and P. P. Foa. Glucose, insulin, pancreatic glucagon and glucagon‐like immunoreactive materials in the plasma of normal and diabetic children. Effect of initial insulin treatment. Horm. Metab. Res. 7: 452–456, 1975.
 121. Matsuyama, T., M., Namba, K. Nonaka, S. Tarui, R. Tanaka, and K. Shima. Decrease in blood glucose and release of gut glucagon‐like immunoreactive materials by bombesin infusion in the dog. Endocrinol. Jpn. 1: 115–119, 1980.
 122. Matsuyama, T., R., Tanaka, K. Shima, and S. Tarui. Anomeric specificity in the response of gut glucagon‐like immunoreactive materials to glucose. Horm. Metab. Res. 11: 214–216, 1979.
 123. Mojsov, S., G., Heinrich, I. B. Wilson, M. Ravazzola, L. Orci, and J. F. Habener. Preproglucagon gene expression in pancreas and intestine diversifies at the level of post‐translational processing. J. Biol. Chem. 261: 11880–11889, 1986.
 124. Moody, A. J. Gut glucagon‐like immunoreactants (GLIs) and other enteric glucagon‐like peptides. J. Clin. Pathol. Lond. 33, Suppl. 8: 58–62, 1980.
 125. Moody, A. J., E. K., Frandsen, H. Jacobsen, F. Sundby, and L. Orci. The structural and immunologic relationship between gut GLI and glucagon. Metabolism 253, Suppl. 1: 1336–1338, 1976.
 126. Moody, A. J., J. J., Holst, L. Thim, and S. Lindkaer‐Jensen. Relationship of glicentin to proglucagon and glucagon in the porcine pancreas. Nature Lond. 289: 514–516, 1981.
 127. Moody, A. J., H., Jacobsen, and F. Sundby. Gastric glucagon and gut glucagon‐like immunoreactants. In: Gut Hormones, edited by S. R. Bloom and J. M. Polak. Edinburgh: Churchill Livingstone, 1978, p. 369–378.
 128. Moody, A. J., and L. Thim. Glucagon, glicentin and related peptides. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. I, p. 139–174.
 129. Moody, A. J., L., Thim, J. J. Holst, and S. Lindkaer‐Jensen. Porcine pancreatic glicentin‐related peptide (Abstract). Diabetologia 19: 300, 1980.
 130. Moxey, P. C., V., Helmstaeder, A. J. Moody, J. C. Garaud, and W. G. Forssman. Glucagon and glicentin immunoreactive cells in human colon. Cell Tissue Res. 221: 483–491, 1982.
 131. Munck, A., A., Kervran, J. C. Marie, D. Bataille, and G. Rosselin. Glucagon‐37 (oxyntomodulin) and glucagon‐29 (pancreatic glucagon) in human bowel: analysis by HPLC and radioreceptorassay. Peptides Fayetteville 5: 553–561, 1984.
 132. Murphy, R. F., K. D., Buchanan, and D. T. Elmore. Isolation of glucagon‐like immunoreactivity of gut by affinity chromatography on anti‐glucagon antibodies coupled to sepharose 4B. Biochim. Biophys. Acta 303: 118–127, 1973.
 133. Mutt, V. Preparation of highly purified secretin. Ark. Kemi 15: 69–74, 1959.
 134. Mutt, V. Further investigation on intestinal hormonal polypeptides. Clin. Endocrinol. Suppl. 5: 175s–183s, 1976.
 135. Mutt, V., J. E., Jorpes, and S. Magnusson. Structure of porcine secretin. The amino acid sequence. Eur. J. Biochem. 15: 513–519, 1970.
 136. Mutt, V., and S. I. Said. Structure of the porcine vasoactive octacosapeptide. The amino acid sequence. Use of kallikrein in its determination. Eur. J. Biochem. 42: 581–589, 1974.
 137. Namba, M., T., Matsuyama, H. Horie, K. Nonaka, and S. Tarui. Inhibition of pancreatic exocrine secretion and augmentation of the release of gut glucagon‐like immunoreactive materials by intraileal administration of bile in the dog. Regul. Pept. 5: 257–262, 1983.
 138. Noe, B. D., C. A., Baste, and G. E. Bauer. Studies on proinsulin and proglucagon biosynthesis at the cellular level. J. Cell Biol. 74: 589–604, 1977.
 139. Noe, B. D., and G. E. Bauer. Evidence for sequential metabolic cleavage of proglucagon to glucagon in glucagon biosynthesis. Endocrinology 97: 868–877, 1975.
 140. O'Connor, F. A., J. M., Conlon, K. Buchanan, and R. F. Murphy. The use of the perfused rat intestine to characterize the immunoreactivity released into serosal secretions following stimulation by glucose. Horm. Metab. Res. 11: 19–23, 1979.
 141. O'Connor, K. J., and N. R. Lazarus. The purification and biological properties of pancreatic big glucagon. Biochem. J. 156: 265–277, 1976.
 142. Ohneda, A., E., Aguilar‐Parada, A. Eisentraut, and R. H. Unger. Control of pancreatic glucagon secretion by glucose. Diabetes 18: 1–10, 1969.
 143. Ohneda, A., K., Horigome, Y. Kai, H. Itabashi, S. Ishii, and S. Yamagata. Purification of canine gut glucagon‐like immunoreactivity (GLI) and its insulin releasing activity. Horm. Metab. Res. 8: 170–174, 1976.
 144. Ohneda, A., T., Kobayashi, and J. Nihei. Response of extra‐pancreatic immunoreactive glucagon to intraluminal nutrients in pancreatectomized dogs. Horm. Metab. Res. 16: 344–348, 1984.
 145. Orci, L., C., Bordi, R. H. Unger, and A. Perrelet. Glucagon‐and glicentin‐producing cells. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. I, p. 57–79.
 146. Orci, L., and A. Perrelet. The morphology of the A‐cell. In: Glucagon: Physiology, Pathophysiology and Morphology of the Pancreatic A‐Cells, edited by R. H. Unger and L. Orci. Amsterdam: Elsevier, 1981, vol. 1, p. 1.
 147. Orci, L., R., Pictet, W. G. Forssmann, A. E. Renold, and C. Rouiller. Structural evidence for glucagon producing cells in the intestinal mucosa of the rat. Diabetologia 4: 56–67, 1968.
 148. Patzelt, C., and E. Schiltz. Conversion of proglucagon in pancreatic alpha cells: the major endproducts are glucagon and a single peptide, the major proglucagon fragment, that contains two glucagon‐like sequences. Proc. Natl. Acad. Sci. USA 81: 5007–5011, 1984.
 149. Patzelt, C., H. S., Tager, R. J. Carroll, and D. F. Steiner. Identification and processing of proglucagon in pancreatic islets. Nature Lond. 282: 260–266, 1979.
 150. Paul, F., F., Misaki, and E. Seifert. Crystalline pancreatic glucagon—a new spasmolytic agent: results of comparative endoscopic and electromanometric investigations in the proximal gastrointestinal tract. Endoscopy 5: 199–204, 1973.
 151. Perez‐Castillo, A., and E. Blázquez. Tissue distribution of glucagon, glucagonlike immunoreactivity, and insulin in the rat. Am. J. Physiol. 238 (Endocrinol. Metab. 1): E258–E266, 1980.
 152. Philippe, J., S., Mojsov, D. J. Drucker, and J. F. Habener. Proglucagon processing in a rat islet cell line resembles phenotype of intestine rather than pancreas. Endocrinology 119: 2833–2839, 1986.
 153. Ravazzola, M., and L. Orci. Glucagon and glicentin immunoreactivity are topologically segregated in the alpha‐granule of the human pancreatic cell line. Nature Lond. 284: 66–67, 1980.
 154. Ravazzola, M., and L. Orci. Transformation of glicentin‐containing L‐cells into glucagon‐containing cells by enzymatic digestion. Diabetes 29: 156–158, 1980.
 155. Ravazzola, M., L., Orci, A. Perrelet, and R. H. Unger. Immunochemical quantitation of glicentin and glucagon during maturation of A‐cell secretory granules (Abstract). Diabetologia 21: 319, 1981.
 156. Ravazzola, M., A., Siperstein, A. J. Moody, F. Sundby, H. Jacobsen, and L. Orci. Glicentin immunoreactive cells: their relationship to glucagon‐producing cells. Endocrinology 105: 499–508, 1979.
 157. Ravazzola, M., R. H., Unger, and L. Orci. Demonstration of glucagon in the stomach of human fetuses. Diabetes 30: 879–882, 1981.
 158. Rehfeld, J. F., and L. G. Heding. Increased release of gut glucagon in reactive hypoglycemia. Br. Med. J. 2: 706–707, 1970.
 159. Rivier, J., J., Spiess, M. Thorner, and W. Vale. Characterization of a growth hormone releasing factor from a human pancreatic tumor. Nature Lond. 300: 276–278, 1982.
 160. Robein, M. J., M. C. De La, Mare, M. Dubrasquet, and S. Bonfils. Utilization of the perfused stomach in anesthetized rats to study the inhibitory effect of somatostatin in gastric acid secretion. Agents Actions 9: 415–421, 1979.
 161. Rodbell, M. The actions of glucagon at its receptor: regulation of adenylate cyclase. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. I, p. 263–290.
 162. Rodbell, M., H. M. J., Krans, S. L. Pohl, and L. Birnbaumer. The glucagon sensitive adenyl cyclase system in plasma membranes of rat liver. III. Binding of glucagon: method of assay and specificity. J. Biol. Chem. 246: 1861–1871, 1971.
 163. Rovira, A., J. M., Novoa‐Lopez, M. Zubiaur, R. Matesanz, M. Ghiglione, J. M. Pascual, and I. Valverde. Renal metabolism of gut glucagon‐like immunoreactivity. Endocrinology 110: 2030–2036, 1982.
 164. Sagor, J. R., M. A., Gathei, M. Y. T. Al‐Mukhtar, N. A. Wright, and S. R. Bloom. Evidence for a humoral mechanism after small intestinal resection. Exclusion of gastrin but not enteroglucagon. Gastroenterology 84: 902–906, 1983.
 165. Sakurai, H., R. E., Dobbs, and R. H. Unger. The effect of somatostatin on the response of GLI to the intraduodenal administration of glucose, protein and fat. Diabetologia 11: 427–430, 1975.
 166. Samols, E., J., Tyler, G. Marri, and V. Marks. Stimulation of glucagon secretion by oral glucose. Lancet 2: 1257–1259, 1965.
 167. Sasaki, H., B., Rubalcava, D. Baetens, E. Blasquez, C. B. Srikant, L. Orci, and R. H. Unger. Identification of glucagon in the gastrointestinal tract. J. Clin. Invest. 56: 135–145, 1975.
 168. Sheikh, S. P., F. G. A., Baldissera, F. O. Karlsen, and J. J. Holst. Glicentin is present in the pig pancreas. FEBS Lett. 179: 1–6, 1985.
 169. Shields, D., T. G., Warren, S. E. Roth, and M. J. Brenner. Cell‐free synthesis and processing of multiple precursors to glucagon. Nature Lond. 289: 511–514, 1981.
 170. Shima, K., N., Sawazaki, S. Morishita, S. Tarui, and M. Nishihawa. Effect of phenformin on the response of plasma intestinal glucagon‐like immunoreactivity to oral glucose in gastrectomized patients. Proc. Soc. Exp. Biol. Med. 150: 232–236, 1975.
 171. Singer, M. V., O. M., Tiscornia, J. P. Mendes De Oliveiro, P. Demol, D. Levesque, and H. Sarles. Effect of glucagon on canine exocrine pancreatic secretion stimulated by a test meal. Can. J. Physiol. Pharmacol. 56: 1–6, 1978.
 172. Srikant, C. B., K., Mccorkle, and R. H. Unger. Properties of immunoreactive glucagon fractions of canine stomach and pancreas. J. Biol. Chem. 252: 1847–1851, 1977.
 173. Srikant, C. B., and R. H. Unger. Evidence for the presence of glucagon‐like immunoreactivity in the pancreas. Endocrinology 99: 1655–1658, 1976.
 174. Stephan, Y., M., Ravazzola, S. Grasso, A. Perrelet, and L. Orci. Glicentin precedes glucagon in the developing human pancreas. Endocrinology 110: 2189–2191, 1982.
 175. Sundby, F., H., Jacobsen, and A. J. Moody. Purification and characterization of a protein from porcine gut with glucagon‐like immunoreactivity. Horm. Metab. Res. 8: 366–371, 1976.
 176. Sundler, F., J., Alumets, J. Holst, L.‐I. Larsson, and R. Håkanson. Ultrastructural identification of cells storing pancreatic‐type glucagon in dog stomach. Histochemistry 50: 33–37, 1976.
 177. Sutherland, E. W., and C. De Duve. Origin and distribution of the hyperglycemic‐glycogenolytic factor of the pancreas. J. Biol Chem. 175: 663–674, 1948.
 178. Tager, H. S. Glucagon‐containing and glucagon‐related peptides: evolutionary, structural and biosynthetic considerations. In: Evolution and Tumor Pathology of the Neuroendocrine System, edited by S. Falkmer, R. Håkanson, and F. Sundler. Amsterdam: Elsevier, 1984, p. 285–311.
 179. Tager, H., M., Hohenboken, J. Markese, and R. J. Dinerstein. Identification and localization of glucagon‐related peptides in rat brain. Proc. Natl. Acad. Sci. USA 77: 6229–6233, 1980.
 180. Tager, H. S., and J. Markese. Intestinal and pancreatic glucagon‐like peptides: evidence for identity of higher molecular weight forms. J. Biol. Chem. 254: 2229–2233, 1979.
 181. Tager, H. S., and D. F. Steiner. Isolation of a glucagon‐containing peptide: primary structure of a possible fragment of proglucagon. Proc. Natl. Acad. Sci. USA 80: 2321–2325, 1973.
 182. Tatemoto, K., and V. Mutt. Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. Nature Lond. 285: 417–418, 1980.
 183. Tatemoto, K., and V. Mutt. Isolation and characterization of the intestinal peptide porcine PHI (PHI‐27), a new member of the glucagon‐secretin family. Proc. Natl. Acad. Sci. USA 78: 6603–6607, 1981.
 184. Thieden, H., J. J., Holst, J. Dich, A. J. Moody, and F. Sundby. Effect of highly purified porcine gut glucagon‐like immunoreactivity (glicentin) on glucose release from isolated rat hepatocytes. Biochim. Biophys. Acta 675: 163–170, 1981.
 185. Thim, L., and A. J. Moody. The primary structure of porcine glicentin (proglucagon). Regul. Pept. 2: 139–150, 1981.
 186. Thim, L., and A. J. Moody. Purification and chemical characterization of a glicentin‐related pancreatic peptide (proglucagon fragment) from porcine pancreas. Biochim. Biophys. Acta. 703: 134–141, 1982.
 187. Thomsen, J., K., Christiansen, and K. Brunfeldt. The amino acid sequence of human glucagon. FEBS Lett. 21: 315–319, 1972.
 188. Tominaga, M., H., Kaneda, S. Marubashi, T. Kamimura, T. Katagiri, and H. Sasaki. Synaptosomal localization and release of glucagon‐like materials in the rat brain. Brain Res. Bull. 12: 373–375, 1984.
 189. Unger, R. H. Glucagon and the insulimglucagon ratio in diabetes and catabolic illnesses. Diabetes 20: 834–838, 1971.
 190. Unger, R. H. Circulating pancreatic glucagon and extra‐pancreatic glucagon‐like materials. In: Handbook of Physiology. Endocrinology, edited by R. O. Greep and E. B. Astwood. Washington, DC: Am. Physiol. Soc., 1972, sect. 7, vol. I, chapt. 34, p. 529–544.
 191. Unger, R. H., E., Aguilar‐Parada, W. Muller, and A. M. Eisentraut. Studies of pancreatic alpha cell function in normal and diabetic subjects. J. Clin. Invest. 49: 837–848, 1970.
 192. Unger, R. H., A. M., Eisentraut, M. S. Mccall, and L. L. Madison. Glucagon antibodies and an immunoassay for glucagon. J. Clin. Invest. 40: 1280–1289, 1961.
 193. Unger, R. H., A. M., Eisentraut, M. S. Mccall, and L. L. Madison. Measurements of endogenous glucagon in plasma and the influence of blood glucose concentration upon its secretion. J. Clin. Invest. 41: 682–689, 1962.
 194. Unger, R. H., H., Ketterer, J. Dupre, and A. M. Eisentraut. Distribution of immunoassayable glucagon in gastrointestinal tissues. Metabolism 15: 865–867, 1966.
 195. Unger, R. H., A., Ohneda, I. Valverde, A. M. Eisentraut, and J. Exton. Characterization of the response of circulating glucagon‐like immunoreactivity to intraduodenal and intravenous administration of glucose. J. Clin. Invest. 47: 48–65, 1968.
 196. Unger, R. H., AND L. Orci (editors), Glucagon: Physiology, Pathophysiology and Morphology of the Pancreatic A‐Cells. Amsterdam: Elsevier, 1981, vol. 2.
 197. Urban, E. WESER Intestinal adaption to bowel resection. Adv. Intern. Med. 26: 261–291, 1980.
 198. Uttenthal, L. O., R. M., Batt, M. W. Carter, and S. R. Bloom. Stimulation of DNA synthesis in cultured small intestine by partially purified enteroglucagon (Abstract). Regul. Pept. 3: 84, 1982.
 199. Uvnäs‐Vallensten, K., L.‐I., Larsson, and C. Johansson. Phosphate buffer stimulates somatostatin release into the antral lumen. Scand. J. Gastroenterol. 14: 797–800, 1979.
 200. Valverde, I. Heterogeneity of circulating glucagon and glucagon‐like immunoreactivity. In: Glucagon, edited by P. J. Lefebvre. Berlin: Springer‐Verlag, 1983, vol. I, p. 223–244.
 201. Valverde, I., M., Ghilione, R. Matesanz, and S. Carado. Chromatographic pattern of gut glucagon‐like immunoreactivity (GLI) in plasma before and during glucose absorption. Horm. Metab. Res. 11: 343–346, 1979.
 202. Valverde, I., D., Rigopoulo, J. Marco, G. R. Faloona, and R. H. Unger. Characterization of glucagon‐like immunoreactivity (GLI). Diabetes 19: 614–623, 1970.
 203. Van Hoorn, W. A. A. I. Vinik, and R. Van Hoorn‐Hickman. The metabolic clearance of endogenous immunoreactive glucagon and exogenous glucagon in pancreatectomized and sham‐operated pigs. Endocrinology 103: 1084–1089, 1978.
 204. Von Heimberg, R. L., and G. A. Hallenbeck. Inhibition of gastric secretion in dogs by glucagon given intraportally. Gastroenterology 47: 531–535, 1964.
 205. Von Mering, J., and O. Minkowski. Diabetes mellitus nach pankreas extirpation. Arch. Exp. Pathol. Pharmakol. 26: 371, 1890.
 206. Walekam, M. J. O., G. J., Murphy, V. J. Hruby, and M. D. Houslay. Activation of two signal‐transduction systems in hepatocytes by glucagon. Nature Lond. 323: 68–71, 1986.
 207. Walsh, J. H. (editor), The brain gut axis: a new frontier. Poceedings of an international symposium held in Florence, Italy, June 29‐July 1, 1981. Peptides Fayetteville 2, Suppl. 2: 1–299, 1981.
 208. Werner, P. L., and J. P. Palmer. Immunoreactive glucagon responses to oral glucose, insulin infusion and deprivation and somatostatin in pancreatectomized man. Diabetes 27: 1005–1012, 1978.
 209. Wider, M. D. Characterization of a heat Stable 12,000 Da, glucagon‐like immunoreactivity (GLI) peptide from porcine ileum that stimulates hepatic glucose production in vivo and in vitro. Proc. Soc. Exp. Biol. Med. 179: 356–364, 1985.
 210. Williamson, R. C. N., and M. Chir. Intestinal adaptation. I. Structural, functional and cytokinetic changes. N. Engl. J. Med. 26: 1393–1402, 1978.
 211. Williamson, R. C. N., and M. Chir. Intestinal adaptation. II. Mechanisms of control. N. Engl. J. Med. 26: 1444–1450, 1978.
 212. Yanaihara, C., T., Matsumoto, Y.‐M. Hong, and N. Yanaihara. Isolation and chemical characterization of glicentin C‐terminal hexapeptide in porcine pancreas. FEBS Lett. 189: 50–56, 1985.
 213. Yanaihara, C., T., Matsumoto, M. Kadowaki, K. Iguchi, and N. Yanaihara. Rat pancreas contains the proglucagon (64–69) fragment and arginine stimulates its release. FEBS Lett. 187: 307–310, 1985.
 214. Yanaihara, N., C., Yanaihara, T. Nishida, S. Mihara, M. Sakagami, J. Ozaki, K. Imagawa, and S. Shin. Synthesis of glicentin‐ and proglucagon‐related peptides and their immunological properties. In: Hormone Receptors in Digestion and Nutrition, edited by G. Rosselin, P. Fromageot, and S. Bonfils. Amsterdam: Elsevier/North‐Holland, 1979, p. 65–68.

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Article Title: Gut Glucagon
 

How to Cite

Dominique Bataille. Gut Glucagon. Compr Physiol 2011, Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology: 455-474. First published in print 1989. doi: 10.1002/cphy.cp060220