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Gene Review

GCG  -  glucagon

Canis lupus familiaris

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Disease relevance of GCG

  • When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis [1].
  • This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin [2].
  • Glucagon: role in the hyperglycemia of diabetes mellitus [2].
  • Despite similar hypoglycemia, sulfated insulin caused greater increment in glucagon [3].
  • We propose that cellular uptake of potassium is enhanced by hyperinsulinemia in ketoacid infusion, and release of potassium results from increased glucagon levels in HCl acidosis [4].

Psychiatry related information on GCG

  • The highest capacity and lowest motor activity was gained when atropine or glucagon was given in cases with detubularized pouch demonstrating an additive effect of the detubularization and drug [5].

High impact information on GCG

  • Glucagon, a polypeptide hormone of 29 amino acids, is synthesized in the islets of Langerhans and immunoreactive forms of the molecule have been found in several tissues [6].
  • Somatostatin perfused in canine pancreases at 10 to 20 picograms per milliliter or 10 to 20 percent of the pancreatic vein somatostatin concentration inhibited insulin and glucagon secretion [7].
  • To investigate the temporal response of the liver to insulin and portal glucose delivery, somatostatin was infused into four groups of 42-h-fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1) [8].
  • Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia [9].
  • Exercise with or without PI was accompanied by four and fivefold increments in norepinephrine and epinephrine respectively, while glucagon (extrapancreatic) fell slightly [10].

Chemical compound and disease context of GCG


Biological context of GCG

  • Dogs serve as an excellent model for studying glycemic control and various aspects of glucagon biology in vivo; however, the amino acid sequence of the dog glucagon receptor has not been reported [15].
  • A repetitive sequence with repeat units (TACACGTA/GCG) that causes the size variation in the D-loop region was also found in both dogs and wolves [16].
  • (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments [17].
  • We also examined the effect of low dose morphine on glucose kinetics independent of changes in the endocrine pancreas by the use of somatostatin plus intraportal replacement of basal insulin and glucagon [11].
  • During pacing of the loop a significant (P less than 0.05-0.01) decrease in the postprandial small intestinal motility index was observed combined with a significant (P less than 0.05) increase in plasma insulin levels, whereas the postprandial increase in glucagon, somatostatin, gastrin, and glucose levels was not different from that in controls [18].

Anatomical context of GCG

  • Adrenergic modulation of pancreatic A, B, and D cells alpha-Adrenergic suppression and beta-adrenergic stimulation of somatostatin secretion, alpha-adrenergic stimulation of glucagon secretion in the perfused dog pancreas [19].
  • Although the tissue responsible for the different kalemic responses could not be defined with certainty, the data are compatible with an hepatic role in response to alterations in the portal vein insulin and/or glucagon levels in both acid infusion studies [4].
  • Opposing actions of glucagon and insulin on splanchnic d cell function [20].
  • Small intestinal motility and plasma levels of insulin, glucagon, gastrin, somatostatin, and glucose were examined during pacing of the residual jejunum or the isolated loop, respectively, compared with control experiments in the same dogs without pacing [18].
  • Different mechanisms of action of vasoactive intestinal polypeptide (VIP) and glucagon on intestinal secretion [21].

Associations of GCG with chemical compounds


Regulatory relationships of GCG


Other interactions of GCG

  • It potently inhibited insulin secretion, less potently inhibited pancreatic somatostatin release and stimulated glucagon secretion, similar to the effects of porcine galanin in the dog [26].
  • RESULTS: A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523 [27].
  • Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert [28].
  • Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs [29].
  • EGF, like glucagon, was still growth stimulatory to the PGE1-independent cells [30].

Analytical, diagnostic and therapeutic context of GCG


  1. Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. Wolfe, R.R., Shaw, J.H., Durkot, M.J. Am. J. Physiol. (1985) [Pubmed]
  2. Glucagon: role in the hyperglycemia of diabetes mellitus. Dobbs, R., Sakurai, H., Sasaki, H., Faloona, G., Valverde, I., Baetens, D., Orci, L., Unger, R. Science (1975) [Pubmed]
  3. Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia. Chap, Z., Ishida, T., Chou, J., Hartley, C.J., Lewis, R.M., Entman, M., Field, J.B. J. Clin. Invest. (1985) [Pubmed]
  4. Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs. Adrogué, H.J., Chap, Z., Ishida, T., Field, J.B. J. Clin. Invest. (1985) [Pubmed]
  5. Effects of atropine, glucagon, and bethanechol on urodynamics of continent cecal urinary reservoir before and after complete, partial, and sham detubularizations in dog. Tammela, T.L., Kiiholma, P.J., Chancellor, M.B. Neurourology and urodynamics. (1993) [Pubmed]
  6. Cell-free synthesis and processing of multiple precursors to glucagon. Shields, D., Warren, T.G., Roth, S.E., Brenner, M.J. Nature (1981) [Pubmed]
  7. Circulating somatostatin acts on the islets of Langerhans by way of a somatostatin-poor compartment. Kawai, K., Ipp, E., Orci, L., Perrelet, A., Unger, R.H. Science (1982) [Pubmed]
  8. Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog. Pagliassotti, M.J., Holste, L.C., Moore, M.C., Neal, D.W., Cherrington, A.D. J. Clin. Invest. (1996) [Pubmed]
  9. Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs. Giacca, A., Fisher, S.J., Shi, Z.Q., Gupta, R., Lickley, H.L., Vranic, M. J. Clin. Invest. (1992) [Pubmed]
  10. Regulation of glucose turnover during exercise in pancreatectomized, totally insulin-deficient dogs. Effects of beta-adrenergic blockade. Bjorkman, O., Miles, P., Wasserman, D., Lickley, L., Vranic, M. J. Clin. Invest. (1988) [Pubmed]
  11. Effects of morphine on glucose homeostasis in the conscious dog. Radosevich, P.M., Williams, P.E., Lacy, D.B., McRae, J.R., Steiner, K.E., Cherrington, A.D., Lacy, W.W., Abumrad, N.N. J. Clin. Invest. (1984) [Pubmed]
  12. Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration. Starke, A., Imamura, T., Unger, R.H. J. Clin. Invest. (1987) [Pubmed]
  13. The defective glucagon response from transplanted intrahepatic pancreatic islets during hypoglycemia is transplantation site-determined. Gupta, V., Wahoff, D.C., Rooney, D.P., Poitout, V., Sutherland, D.E., Kendall, D.M., Robertson, R.P. Diabetes (1997) [Pubmed]
  14. Putative hypothalamic glucoreceptors play no essential role in the response to moderate hypoglycemia. Cane, P., Artal, R., Bergman, R.N. Diabetes (1986) [Pubmed]
  15. Cloning and expression of canine glucagon receptor and its use to evaluate glucagon receptor antagonists in vitro and in vivo. Yang, X., Yates, M.L., Candelore, M.R., Feeney, W., Hora, D., Kim, R.M., Parmee, E.R., Berger, J.P., Zhang, B.B., Qureshi, S.A. Eur. J. Pharmacol. (2007) [Pubmed]
  16. Extensive interbreeding occurred among multiple matriarchal ancestors during the domestication of dogs: evidence from inter- and intraspecies polymorphisms in the D-loop region of mitochondrial DNA between dogs and wolves. Tsuda, K., Kikkawa, Y., Yonekawa, H., Tanabe, Y. Genes Genet. Syst. (1997) [Pubmed]
  17. The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs. Vranic, M., Kawamori, R., Pek, S., Kovacevic, N., Wrenshall, G.A. J. Clin. Invest. (1976) [Pubmed]
  18. Effect of enteric pacing on intestinal motility and hormone secretion in dogs with short bowel. Reiser, S.B., Schusdziarra, V., Bollschweiler, E., Hölscher, A.H., Siewert, J.R. Gastroenterology (1991) [Pubmed]
  19. Adrenergic modulation of pancreatic A, B, and D cells alpha-Adrenergic suppression and beta-adrenergic stimulation of somatostatin secretion, alpha-adrenergic stimulation of glucagon secretion in the perfused dog pancreas. Samols, E., Weir, G.C. J. Clin. Invest. (1979) [Pubmed]
  20. Opposing actions of glucagon and insulin on splanchnic d cell function. Kawai, K., Unger, R.H. J. Clin. Invest. (1983) [Pubmed]
  21. Different mechanisms of action of vasoactive intestinal polypeptide (VIP) and glucagon on intestinal secretion. Mailman, D. Gastroenterology (1977) [Pubmed]
  22. Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones. Ionut, V., Hucking, K., Liberty, I.F., Bergman, R.N. Diabetologia (2005) [Pubmed]
  23. Factors controlling gastric-glucagon release. Lefèbvre, P.J., Luyckx, A.S. J. Clin. Invest. (1977) [Pubmed]
  24. Effects of cyclooxygenase-2 inhibitor on glucagon-induced delayed gastric emptying and gastric dysrhythmia in dogs. Xu, J., Chen, J.D. Neurogastroenterol. Motil. (2007) [Pubmed]
  25. Dissociation between renal prostaglandin E2 and renin release. Effects of glucagon, dopamine and cyclic AMP in dogs. Vikse, A., Bugge, J., Dahl, E., Kiil, F. Acta Physiol. Scand. (1985) [Pubmed]
  26. Canine galanin: sequence, expression and pancreatic effects. Boyle, M.R., Verchere, C.B., McKnight, G., Mathews, S., Walker, K., Taborsky, G.J. Regul. Pept. (1994) [Pubmed]
  27. Effect of nonpeptide motilin agonist EM523 on release of gut and pancreatic hormones in conscious dogs. Shiba, Y., Mizumoto, A., Satoh, M., Inui, A., Itoh, Z., Omura, S. Gastroenterology (1996) [Pubmed]
  28. Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula. Francavilla, A., Starzl, T.E., Porter, K., Foglieni, C.S., Michalopoulos, G.K., Carrieri, G., Trejo, J., Azzarone, A., Barone, M., Zeng, Q.H. Hepatology (1991) [Pubmed]
  29. Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs. Fung, L.C., Chisholm, C., Greenberg, G.R. Endocrinology (1998) [Pubmed]
  30. PGE1-independent MDCK cells have elevated intracellular cyclic AMP but retain the growth stimulatory effects of glucagon and epidermal growth factor in serum-free medium. Taub, M., Devis, P.E., Grohol, S.H. J. Cell. Physiol. (1984) [Pubmed]
  31. Retrograde perfusion as a model for testing the relative effects of glucose versus insulin on the A cell. Stagner, J.I., Samols, E. J. Clin. Invest. (1986) [Pubmed]
  32. Pancreatic hormone profiles and metabolism posthepatectomy in the dog. Evidence for a hepatotrophic role of insulin, glucagon, and pancreatic polypeptide. Cohen, D.M., Jaspan, J.B., Polonsky, K.S., Lever, E.G., Moossa, A.R. Gastroenterology (1984) [Pubmed]
  33. Wearable artificial endocrine pancrease with needle-type glucose sensor. Shichiri, M., Kawamori, R., Yamasaki, Y., Hakui, N., Abe, H. Lancet (1982) [Pubmed]
  34. Identification of distinct receptor complexes that account for high-and low-affinity glucagon binding to hepatic plasma membranes. Mason, J.C., Tager, H.S. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
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