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Gene Review

GCG  -  glucagon

Bos taurus

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Disease relevance of GCG

  • Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS). Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor [1].
  • In contrast, the rise in plasma pancreatic glucagon concentration during less intense hypoxia was abolished by autonomic blockade [2].
  • A cloned line of canine kidney cells (MDCK) transformed with Harvey murine sarcoma virus, in contrast to the parental, untransformed line, expressed glucagon sensitivity only under controlled culture conditions [3].
  • 4. Hypercapnia produced by inhalation of either 5% or 10% CO2 for 30 min stimulated maximal release of adrenal glucocorticoids and caused a substantial rise in plasma glucagon concentration [2].
  • Glucagon and aminophylline as pulmonary vasodilators in the calf with hypoxic pulmonary hypertension [4].

High impact information on GCG

  • Although an increase in lipolysis is seen with norepinephrine and growth hormone after insulin treatment, other lipolytic agents such as ACTH, thyrotropin, and glucagon evoke similar responses in insulin-treated and control cells [5].
  • The enzyme hydrolyzed about 2 molecules of ATP for each new amino group generated with casein, bovine serum albumin, glucagon, or guanidinated casein as substrates, even though these proteins differ up to 20-fold in size and 3-4 fold in rates of hydrolysis of peptide bonds [6].
  • Furthermore, other peptide hormones such as angiotensin II, glucagon, or insulin are ineffective in competing for 125I-ANF binding and cross-linking to the receptor [7].
  • The activation phenomenon was not mimicked by insulin A or B chains, somatostatin, glucagon, or bovine serum albumin, and could be prevented by insulin antiserum [8].
  • Large glucagon immunoreactive substances, extracted from the fetal bovine pancreas and separated by gel filtration in the presence of 6 M guanidinium-hydrochloride, were submitted to lectin-sepharose affinity column chromatograph [9].

Chemical compound and disease context of GCG


Biological context of GCG


Anatomical context of GCG

  • Gel-filtered peak I (approximately 45 K delta) and peak II (approximately 10 K delta) interacted biospecifically with concanavalin-A- and wheat-germ-lectin-sepharoses, suggesting glycoproteins as possible constituents of large glucagon immunoreactive substances in extracts of the fetal bovine pancreas [9].
  • Conclusions: (1) pancreatic alpha cells respond more rapidly than beta cells to the same stimulus; (2) antecedent release of glucagon is not the principal mediator of insulin release in response to stimuli common to both hormones; and (3) endogenous glucagon may at best modify the release of insulin evoked by certain secretagogues [19].
  • Equimolar mixtures of glucagon with insulin from 10(-15)-10(-7) M increased the fraction of hepatocytes synthesizing DNA first at 4-8 h, and then at 20-24 h [20].
  • Certain pharmacological characteristics of the release of pancreatic glucagon in response to stimulation of the splanchnic nerves [21].
  • 2. Moderate hypoglycaemia for a limited period (0-1 u. insulin/kg), elicited a prompt increase in steroid output from the adrenal gland followed by a significant rise in plasma glucagon concentration [22].

Associations of GCG with chemical compounds

  • A determination of the spatial structure of the polypeptide hormone glucagon bound to perdeuterated dodecylphosphocholine micelles is described [14].
  • Conclusions: (a) Diazoxide inhibits the secretion of glucagon as well as insulin in response to certain secretagogues independent of any changes in prevailing levels of glucose [23].
  • Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins [15].
  • Five secretagogues of both glucagon and insulin--10 mM L-arginine, 5 mM L-leucine, 1.4 muM prostaglandin F2alpha, 100 nM bovine growth hormone, and 10 nM theophylline--were administered individually in the presence or absence of 325 muM diazoxide [23].
  • Basal secretion of glucagon or insulin was not discernibly affected by diazoxide [23].

Other interactions of GCG

  • In contrast, insulin or glucagon alone had no effect on production of the IGFBP-4 by thecal cells but when combined inhibited IGFBP-4 production [24].
  • In Experiment 3A, insulin enhanced production of IGFBP-5 by thecal cells whereas glucagon blocked insulin's stimulatory effect [24].
  • Fasting concentrations of IGF-II and glucagon were not affected (P > 0.05) by obesity [25].
  • PACAP, when infused together with acetylcholine, also stimulated the release of pancreatic glucagon in the absence of exogenous glucose but not in its presence [26].
  • 5. Inhibition of binding of tritiated hormone by unlabeled PTH was also highly effective at pH 6.0, but this apparently specific binding was also inhibited by adrenocorticotropic hormone, insulin, glucagon, and vasopressin [27].

Analytical, diagnostic and therapeutic context of GCG

  • Primary sequence analysis of one clone containing a 1,200-base-pair DNA insert revealed that it contained an essentially full-length copy of glucagon mRNA [28].
  • The glucagon-like immunochemical identity of the lectin-sepharose-bound substances was further substantiated by binding to antiglucagon antibodies-sepharose and by characteristic proportional dilutions in the glucagon radioimmunoassay [9].
  • The rise in mean plasma glucagon concentration in response to GRP that occurred in the control group, the group pre-treated with amino acids alone and the group given both glucose and amino acids, was virtually eliminated in the group pre-treated with glucose alone [29].
  • The product was homogeneous and indistinguishable from natural bovine glucagon by gel electrophoresis, ion-exchange chromatography, reverse-phase high-pressure liquid chromatography, fluorescence spectroscopy, and amino acid analysis [30].
  • 3. During BSA-free perfusion, high dose troglitazone increased basal (P < 0.01), but inhibited glucagon-stimulated incremental glucose production by approximately 75% (10.0 +/- 2.5 vs control: 40.0 +/- 7.2 micromol g liver(-1), P < 0.01) [31].


  1. Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS). Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor. Labrecque, D.R., Wilson, M., Fogerty, S. Exp. Cell Res. (1984) [Pubmed]
  2. Adrenal and pancreatic endocrine responses to hypoxia and hypercapnia in the calf. Bloom, S.R., Edwards, A.V., Hardy, R.N. J. Physiol. (Lond.) (1977) [Pubmed]
  3. Expression of glucagon sensitivity by transformed MDCK cells normally unresponsive to glucagon: early commitment to differentiation. Beckner, S.K., Lin, M.C. J. Cell. Physiol. (1985) [Pubmed]
  4. Glucagon and aminophylline as pulmonary vasodilators in the calf with hypoxic pulmonary hypertension. Bisgard, G.E., Will, J.A. Chest (1977) [Pubmed]
  5. Chronic exposure of rat fat cells to insulin enhances lipolysis and activation of partially purified hormone-sensitive lipase. Kang, E.S., Betts, D., Fain, J.N., Bahouth, S.W., Myers, L.K. Diabetes (1993) [Pubmed]
  6. The energy utilized in protein breakdown by the ATP-dependent protease (La) from Escherichia coli. Menon, A.S., Waxman, L., Goldberg, A.L. J. Biol. Chem. (1987) [Pubmed]
  7. Identification of the receptor for atrial natriuretic factor on cultured vascular cells. Schenk, D.B., Phelps, M.N., Porter, J.G., Scarborough, R.M., McEnroe, G.A., Lewicki, J.A. J. Biol. Chem. (1985) [Pubmed]
  8. A novel in vitro interaction of insulin with rabbit skeletal muscle protein phosphatases. Speth, M., Lee, E.Y. J. Biol. Chem. (1984) [Pubmed]
  9. Glycoprotein-like large glucagon immunoreactive species in extracts of the fetal bovine pancreas. Tung, A.K., Cockburn, E., Siu, K.P. Diabetes (1982) [Pubmed]
  10. Adrenal and pancreatic endocrine responses to hypoxia in the conscious calf. Bloom, S.R., Edwards, A.V., Hardy, R.N., Silver, M. J. Physiol. (Lond.) (1976) [Pubmed]
  11. The role of the autonomic nervous system in the control of glucagon, insulin and pancreatic polypeptide release from the pancreas. Bloom, S.R., Edwards, A.V., Hardy, R.N. J. Physiol. (Lond.) (1978) [Pubmed]
  12. The metabolic and hormonal adaptations of normal dogs to long-term exogenous sulfated insulin infusions. Nomura, M., Greenberg, G.R., Bahoric, A., Albisser, A.M. Metab. Clin. Exp. (1986) [Pubmed]
  13. The glucagon receptor and adenylate cyclase. Levey, G.S. Metab. Clin. Exp. (1975) [Pubmed]
  14. Conformation of glucagon in a lipid-water interphase by 1H nuclear magnetic resonance. Braun, W., Wider, G., Lee, K.H., Wüthrich, K. J. Mol. Biol. (1983) [Pubmed]
  15. Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. Miller, L.L. Diabetes (1976) [Pubmed]
  16. Adrenal cortex mitochondrial enzyme with ATP-dependent protease and protein-dependent ATPase activities. Purification and properties. Watabe, S., Kimura, T. J. Biol. Chem. (1985) [Pubmed]
  17. Effect of bovine pancreatic polypeptide on isolated rat liver cells. Schwartz, S.S., Corkey, B., Williamson, J.R., Rubenstein, A.H. Endocrinology (1980) [Pubmed]
  18. Characterization of insulins and proglucagon-derived peptides from a phylogenetically ancient fish, the paddlefish (Polyodon spathula). Nguyen, T.M., Mommsen, T.P., Mims, S.M., Conlon, J.M. Biochem. J. (1994) [Pubmed]
  19. Glucagon release precedes insulin release in response to common secretagogues. Pek, S., Tai, T.Y., Crowther, R., Fajans, S.S. Diabetes (1976) [Pubmed]
  20. Effect of glucagon and insulin on the growth of neonatal rat hepatocytes in primary tissue culture. Armato, U., Draghi, E., Andreis, P.G. Endocrinology (1978) [Pubmed]
  21. Certain pharmacological characteristics of the release of pancreatic glucagon in response to stimulation of the splanchnic nerves. Bloom, S.R., Edwards, A.V. J. Physiol. (Lond.) (1978) [Pubmed]
  22. Endocrine responses to insulin hypoglycaemia in the young calf. Bloom, S.R., Edwards, A.V., Hardy, R.N., Malinowska, K.W., Silver, M. J. Physiol. (Lond.) (1975) [Pubmed]
  23. Inhibition of glucagon secretion by diazoxide in vitro. Urdanivia, E., Pek, S., Santiago, J.C. Diabetes (1979) [Pubmed]
  24. Hormonal control of ovarian cell production of insulin-like growth factor binding proteins. Chamberlain, C.S., Spicer, L.J. Mol. Cell. Endocrinol. (2001) [Pubmed]
  25. Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep. McCann, J.P., Loo, S.C., Aalseth, D.L., Abribat, T. J. Endocrinol. (1997) [Pubmed]
  26. Pancreatic endocrine responses to the peptides VIP and PACAP in the conscious calf. Edwards, A.V., Bloom, S.R., Ghatei, M.A. Exp. Physiol. (1997) [Pubmed]
  27. Binding of tritiated bovine parathyroid hormone to plasma membranes from bovine kidney cortex. Zull, J.E., Malbon, C.C., Chuang, J. J. Biol. Chem. (1977) [Pubmed]
  28. Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Lopez, L.C., Frazier, M.L., Su, C.J., Kumar, A., Saunders, G.F. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  29. Effects of certain metabolites on pancreatic endocrine responses to gastrin-releasing peptide in conscious calves. Bloom, S.R., Edwards, A.V., Ghatei, M.A. J. Physiol. (Lond.) (1984) [Pubmed]
  30. Solid-phase synthesis of crystalline glucagon. Mojsov, S., Merrifield, R.B. Biochemistry (1981) [Pubmed]
  31. Acute troglitazone action in isolated perfused rat liver. Preininger, K., Stingl, H., Englisch, R., Fürnsinn, C., Graf, J., Waldhäusl, W., Roden, M. Br. J. Pharmacol. (1999) [Pubmed]
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