More information on this family may be found on the IUPHAR-DB family and introduction pages.
The glucagon family of receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on the Glucagon receptor family, [12]) are activated by the endogenous peptide (27–44 aa) hormones glucagon, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide or GIP, ENSG00000159224), growth hormone-releasing hormone (GHRH, ENSG00000118702) and secretin (ENSG00000070031). One common precursor (ENSG00000115263) generates glucagon, GLP-1 and GLP-2 peptides [9].
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Authier, F; Desbuquois, B. (2008) Glucagon receptors. Cell. Mol. Life Sci., 65 (12): 1880-99. [PMID:18292967]
Burcelin, R; Serino, M; Cabou, C. (2009) A role for the gut-to-brain GLP-1-dependent axis in the control of metabolism. Curr Opin Pharmacol, 9 (6): 744-52. [PMID:19800290]
De Block, CE; Van Gaal, LF. (2009) GLP-1 receptor agonists for type 2 diabetes. Lancet, 374 (9683): 4-6. [PMID:19515414]
Doyle, ME; Egan, JM. (2007) Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol. Ther., 113 (3): 546-93. [PMID:17306374]
Dubé, PE; Brubaker, PL. (2007) Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am. J. Physiol. Endocrinol. Metab., 293 (2): E460-5. [PMID:17652153]
Frezza, EE; Wachtel, MS; Chiriva-Internati, M. (2007) The multiple faces of glucagon-like peptide-1--obesity, appetite, and stress: what is next? A review. Dig. Dis. Sci., 52 (3): 643-9. [PMID:17268838]
Hayes, MR; De Jonghe, BC; Kanoski, SE. (2010) Role of the glucagon-like-peptide-1 receptor in the control of energy balance. Physiol. Behav., 100 (5): 503-10. [PMID:20226203]
Holst, JJ. (2007) The physiology of glucagon-like peptide 1. Physiol. Rev., 87 (4): 1409-39. [PMID:17928588]
Holst, JJ; Deacon, CF; Vilsbøll, T; Krarup, T; Madsbad, S. (2008) Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med, 14 (4): 161-8. [PMID:18353723]
Markovic, D; Grammatopoulos, DK. (2009) Focus on the splicing of secretin GPCRs transmembrane-domain 7. Trends Biochem. Sci., 34 (9): 443-52. [PMID:19733082]
Mayo, KE; Miller, LJ; Bataille, D; Dalle, S; Göke, B; Thorens, B; Drucker, DJ. (2003) International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol. Rev., 55 (1): 167-94. [PMID:12615957]
Miller, LJ; Dong, M; Harikumar, KG. (2011) Ligand Binding and Activation of the Secretin Receptor, a Prototypic Family B G Protein-Coupled Receptor. Br J Pharmacol, [Epub ahead of print]. [PMID:21542831]
Nauck, MA. (2009) Unraveling the science of incretin biology. Am. J. Med., 122 (6 Suppl): S3-S10. [PMID:19464426]
Nauck, MA; Vardarli, I; Deacon, CF; Holst, JJ; Meier, JJ. (2011) Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?. Diabetologia, 54 (1): 10-8. [PMID:20871975]
Schally, AV; Varga, JL; Engel, JB. (2008) Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab, 4 (1): 33-43. [PMID:18084344]
St-Pierre, DH; Broglio, F. (2010) Secretin: Should we revisit its metabolic outcomes?. J. Endocrinol. Invest., 33 (4): 266-75. [PMID:20503484]
Verspohl, EJ. (2009) Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol. Ther., 124 (1): 113-38. [PMID:19545590]
Vrang, N; Larsen, PJ. (2010) Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Prog. Neurobiol., 92 (3): 442-62. [PMID:20638440]
Williams, DL. (2009) Minireview: finding the sweet spot: peripheral versus central glucagon-like peptide 1 action in feeding and glucose homeostasis. Endocrinology, 150 (7): 2997-3001. [PMID:19389830]
1. Boulanger, L; Girard, N; Strecko, J; Gaudreau, P. (2002) Characterization of a growth hormone-releasing hormone binding site in the rat renal medulla. Peptides, 23 (1): 43-50. [PMID:11814616]
2. Cascieri, MA; Koch, GE; Ber, E; Sadowski, SJ; Louizides, D; de Laszlo, SE; Hacker, C; Hagmann, WK; MacCoss, M; Chicchi, GG; et al.. (1999) Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor. J. Biol. Chem., 274 (13): 8694-7. [PMID:10085108]
3. Chow, B. K. (1995) Molecular cloning and functional characterization of a human secretin receptor. Biochem. Biophys. Res. Commun., 212: 204-211. [PMID:7612008]
4. Christopoulos, A., Christopoulos, G., Morfis, M., Udawela, M., Laburthe, M., Couvineau, A., Kuwasako, K., Tilakaratne, N. and Sexton, P.M. (2003) Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem., 278: 3293-3297. [PMID:12446722]
5. Coy, D. H. and Murphy, W. A. (1996) Structural simplification of potent growth hormone-releasing hormone analogs: implications for other members of the VIP/GHRH/PACAP family. Ann. N.Y. Acad. Sci., 805: 149-158. [PMID:8993400]
6. Dillon, JS; Tanizawa, Y; Wheeler, MB; Leng, XH; Ligon, BB; Rabin, DU; Yoo-Warren, H; Permutt, MA; Boyd, AE. (1993) Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor. Endocrinology, 133 (4): 1907-10. [PMID:8404634]
7. Gallwitz, B., Witt, M., Morys-Wortmann, C., Folsch, U. R. and Schmidt, W. E. (1996) GLP-1/GIP chimeric peptides define the structural requirements for specific ligand-receptor interaction of GLP-1. Regul Pept, 63: 17-22. [PMID:8795084]
8. Haffar, BM; Hocart, SJ; Coy, DH; Mantey, S; Chiang, HC; Jensen, RT. (1991) Reduced peptide bond pseudopeptide analogues of secretin. A new class of secretin receptor antagonists. J. Biol. Chem., 266 (1): 316-22. [PMID:1702423]
9. Irwin, DM. (2001) Molecular evolution of proglucagon. Regul. Pept., 98 (1-2): 1-12. [PMID:11179772]
10. Jorgensen, R., Martini, L., Schwartz, T. W. and Elling, C. E. (2005) Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype. Mol Endocrinol, 19: 812-823. [PMID:15528268]
11. Madsen, P; Knudsen, LB; Wiberg, FC; Carr, RD. (1998) Discovery and structure-activity relationship of the first non-peptide competitive human glucagon receptor antagonists. J. Med. Chem., 41 (26): 5150-7. [PMID:9857085]
12. Mayo, KE; Miller, LJ; Bataille, D; Dalle, S; Göke, B; Thorens, B; Drucker, DJ. (2003) International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol. Rev., 55 (1): 167-94. [PMID:12615957]
13. Petersen, KF; Sullivan, JT. (2001) Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia, 44 (11): 2018-24. [PMID:11719833]
14. Pohl, S. L., Birnbaumer, L. and Rodbell, M. (1969) Glucagon-sensitive adenyl cylase in plasma membrane of hepatic parenchymal cells. Science, 164: 566-567. [PMID:4305077]
15. Raufman, JP; Singh, L; Eng, J. (1991) Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9-39) amide, a specific exendin receptor antagonist. J. Biol. Chem., 266 (5): 2897-902. [PMID:1704369]
16. Schally, A. V. and Varga, J. L. (1999) Antagonistic analogs of growth hormone-releasing hormone: new potential antitumor agents. Trends Endocrinol. Metab., 10: 383-391. [PMID:10542394]
17. Thulesen, J., Knudsen, L. B., Hartmann, B., Hastrup, S., Kissow, H., Jeppesen, P. B., Orskov, C., Holst, J. J. and Poulsen, S. S. (2002) The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul Pept, 103: 9-15. [PMID:11738243]
18. Tibaduiza, EC; Chen, C; Beinborn, M. (2001) A small molecule ligand of the glucagon-like peptide 1 receptor targets its amino-terminal hormone binding domain. J. Biol. Chem., 276 (41): 37787-93. [PMID:11498540]
19. Unson, C. and Merrifield, R. B. (1987) Synthetic peptide antagonists of glucagon. Proc. Natl. Acad. Sci. U.S.A., 84: 4083-4087. [PMID:3035568]
20. Unson, CG; Gurzenda, EM; Merrifield, RB. (1989) Biological activities of des-His1[Glu9]glucagon amide, a glucagon antagonist. Peptides, 10 (6): 1171-7. [PMID:2560175]
21. Varga, J. L. and Rekasi, Z. (1999) Synthesis and biological evaluation of antagonists of growth hormone- releasing hormone with high and protracted in vivo activities. Proc. Natl. Acad. Sci. U.S.A, 96: 692-697. [PMID:9892695]
22. Varga, J. L., Schally, A. V., Horvath, J. E., Kovacs, M., Halmos, G., Groot, K., Toller, G. L., Rekasi, Z. and Zarandi, M. (2004) Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10. Proc Natl Acad Sci U S A, 101: 1708-1713. [PMID:14755056]
23. Volz, A., Goke, R., Lankat-Buttgereit, B., Fehmann, H. C., Bode, H. P. and Goke, B. (1995) Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. FEBS Lett, 373: 23-29. [PMID:7589426]
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The glucagon receptor has been reported to interact with receptor activity modifying proteins (RAMPs), specifically RAMP2, in heterologous expression systems [4], although the physiological significance of this has yet to be established.