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Gene Review

GCGR  -  glucagon receptor

Homo sapiens

Synonyms: GGR, GL-R, Glucagon receptor
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Disease relevance of GCGR


High impact information on GCGR


Chemical compound and disease context of GCGR


Biological context of GCGR


Anatomical context of GCGR


Associations of GCGR with chemical compounds

  • The glucose-lowering effects of glucagon peptide antagonists and antiglucagon neutralising antibodies first demonstrated the potential of glucagon receptor (GCGR) antagonism as a treatment for hyperglycaemia [18].
  • Basal cyclase activity, as well as the activity after stimulation with glucagon or with agents (i.e., sodium fluoride and forskolin) that act beyond the glucagon receptor, was significantly decreased (p less than 0.05, p less than 0.001 respectively) [19].
  • One major difference was observed between the glucagon receptor in tumor tissue and that in liver and heart, namely, a marked lability in 125-I-glucagon binding and adenylate cyclase activity [3].
  • The cDNA encodes a receptor protein with 80% identity to rat GGR that binds [125I]glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate [14].
  • The glucagon receptor was functionally coupled to increases in cyclic AMP in S2 cells [20].

Physical interactions of GCGR

  • In addition, the glucagon receptor core domain (7TM helices and connecting loops) strongly determines specificity for the glucagon amino terminus [21].

Enzymatic interactions of GCGR

  • Therefore, these results reveal that within hepatic target cells and consequent to glucagon-mediated internalization of the serine-phosphorylated glucagon receptor and the Gsalpha protein, extended signal transduction may occur in vivo at the locus of the endo-lysosomal apparatus [16].

Regulatory relationships of GCGR


Other interactions of GCGR


Analytical, diagnostic and therapeutic context of GCGR


  1. Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant. Strazzullo, P., Iacone, R., Siani, A., Barba, G., Russo, O., Russo, P., Barbato, A., D'Elia, L., Farinaro, E., Cappuccio, F.P. J. Mol. Med. (2001) [Pubmed]
  2. A linkage and cross-sectional study of hypertension and obesity using a poly (A) Alu-repeat polymorphism at the glucagon receptor gene locus (17q25). Rutherford, S., Boatwright, S.D., Samwell, G.A., Morris, B.J., Griffiths, L.R. Clin. Exp. Pharmacol. Physiol. (1998) [Pubmed]
  3. Characterization of the glucagon receptor in a pheochromocytoma. Levey, G.S., Weiss, S.R., Ruiz, E. J. Clin. Endocrinol. Metab. (1975) [Pubmed]
  4. A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. Hager, J., Hansen, L., Vaisse, C., Vionnet, N., Philippi, A., Poller, W., Velho, G., Carcassi, C., Contu, L., Julier, C. Nat. Genet. (1995) [Pubmed]
  5. A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus. Fujisawa, T., Ikegami, H., Yamato, E., Takekawa, K., Nakagawa, Y., Hamada, Y., Ueda, H., Fukuda, M., Ogihara, T. Diabetologia (1995) [Pubmed]
  6. Glucagon receptor gene mutation in essential hypertension. Chambers, S.M., Morris, B.J. Nat. Genet. (1996) [Pubmed]
  7. Hypoglycemia leads to age-related loss of vision. Umino, Y., Everhart, D., Solessio, E., Cusato, K., Pan, J.C., Nguyen, T.H., Brown, E.T., Hafler, R., Frio, B.A., Knox, B.E., Engbretson, G.A., Haeri, M., Cui, L., Glenn, A.S., Charron, M.J., Barlow, R.B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Mutation of the glucagon receptor gene and diabetes mellitus in the UK: association or founder effect? Gough, S.C., Saker, P.J., Pritchard, L.E., Merriman, T.R., Merriman, M.E., Rowe, B.R., Kumar, S., Aitman, T., Barnett, A.H., Turner, R.C. Hum. Mol. Genet. (1995) [Pubmed]
  9. Design of a Long Acting Peptide Functioning as Both a Glucagon-like Peptide-1 Receptor Agonist and a Glucagon Receptor Antagonist. Pan, C.Q., Buxton, J.M., Yung, S.L., Tom, I., Yang, L., Chen, H., Macdougall, M., Bell, A., Claus, T.H., Clairmont, K.B., Whelan, J.P. J. Biol. Chem. (2006) [Pubmed]
  10. Hypothesis: glucagon receptor glycine to serine missense mutation contributes to one in 20 cases of essential hypertension. Morris, B.J., Chambers, S.M. Clin. Exp. Pharmacol. Physiol. (1996) [Pubmed]
  11. Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes. Parker, J.C., McPherson, R.K., Andrews, K.M., Levy, C.B., Dubins, J.S., Chin, J.E., Perry, P.V., Hulin, B., Perry, D.A., Inagaki, T., Dekker, K.A., Tachikawa, K., Sugie, Y., Treadway, J.L. Diabetes (2000) [Pubmed]
  12. Localization of the glucagon receptor gene to human chromosome band 17q25. Menzel, S., Stoffel, M., Espinosa, R., Fernald, A.A., Le Beau, M.M., Bell, G.I. Genomics (1994) [Pubmed]
  13. Human pheochromocytomas, but not adrenal medulla, express glucagon-receptor gene and possess an in vitro secretory response to glucagon. Albertin, G., Aragona, F., Gottardo, L., Malendowicz, L.K., Nussdorfer, G.G. Peptides (2001) [Pubmed]
  14. The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization. Lok, S., Kuijper, J.L., Jelinek, L.J., Kramer, J.M., Whitmore, T.E., Sprecher, C.A., Mathewes, S., Grant, F.J., Biggs, S.H., Rosenberg, G.B. Gene (1994) [Pubmed]
  15. Cloning and expression of a human glucagon receptor. MacNeil, D.J., Occi, J.L., Hey, P.J., Strader, C.D., Graziano, M.P. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  16. Glucagon-mediated internalization of serine-phosphorylated glucagon receptor and Gsalpha in rat liver. Merlen, C., Fabrega, S., Desbuquois, B., Unson, C.G., Authier, F. FEBS Lett. (2006) [Pubmed]
  17. Cloning and characterization of the glucagon receptor from cynomologous monkey. McNally, T., Grihalde, N.D., Pederson, T.M., Ogiela, C.A., Djuric, S.W., Collins, C.A., Lin, C.W., Reilly, R.M. Peptides (2004) [Pubmed]
  18. Glucagon as a target for the treatment of Type 2 diabetes. Sloop, K.W., Michael, M.D., Moyers, J.S. Expert Opin. Ther. Targets (2005) [Pubmed]
  19. Altered action of glucagon on human liver in type 2 (non-insulin-dependent) diabetes mellitus. Arner, P., Einarsson, K., Ewerth, S., Livingston, J.N. Diabetologia (1987) [Pubmed]
  20. Interaction of [fluorescein-Trp25]glucagon with the human glucagon receptor expressed in Drosophila Schneider 2 cells. Tota, M.R., Xu, L., Sirotina, A., Strader, C.D., Graziano, M.P. J. Biol. Chem. (1995) [Pubmed]
  21. Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus. Runge, S., Gram, C., Brauner-Osborne, H., Madsen, K., Knudsen, L.B., Wulff, B.S. J. Biol. Chem. (2003) [Pubmed]
  22. Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Huypens, P., Ling, Z., Pipeleers, D., Schuit, F. Diabetologia (2000) [Pubmed]
  23. Determinants for calcitonin analog interaction with the calcitonin receptor N-terminus and transmembrane-loop regions. Stroop, S.D., Nakamuta, H., Kuestner, R.E., Moore, E.E., Epand, R.M. Endocrinology (1996) [Pubmed]
  24. Glucagon induces a rapid and sustained phosphorylation of the human glucagon receptor in Chinese hamster ovary cells. Heurich, R.O., Buggy, J.J., Vandenberg, M.T., Rossomando, A.J. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  25. New approaches in the treatment of type 2 diabetes. Zhang, B.B., Moller, D.E. Current opinion in chemical biology. (2000) [Pubmed]
  26. Glucagon-induced self-association of recombinant proteins in Escherichia coli and affinity purification using a fragment of glucagon receptor. Kim, D.Y., Lee, J., Saraswat, V., Park, Y.H. Biotechnol. Bioeng. (2000) [Pubmed]
  27. Glucagon does not affect catecholamine release in primary cultures of bovine adrenal chromaffin cells. Sharabi, Y., Zimlichman, R., Alesci, S., Huynh, T., Mansouri, R., Chun, J., Perera, S., Pacak, K., Goldstein, D.S. Horm. Metab. Res. (2005) [Pubmed]
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