Glucagon receptor
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Glucagon receptor | |||||||||||||
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Identifiers | |||||||||||||
Symbols | GCGR; GGR; MGC138246 | ||||||||||||
External IDs | OMIM: 138033 MGI: 99572 HomoloGene: 131 IUPHAR: glucagon GeneCards: GCGR Gene | ||||||||||||
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Orthologs | |||||||||||||
Species | Human | Mouse | |||||||||||
Entrez | 2642 | 14527 | |||||||||||
Ensembl | ENSG00000215644 | ENSMUSG00000025127 | |||||||||||
UniProt | P47871 | Q3UN81 | |||||||||||
RefSeq (mRNA) | NM_000160 | NM_008101 | |||||||||||
RefSeq (protein) | NP_000151 | NP_032127 | |||||||||||
Location (UCSC) | Chr 17: 79.76 - 79.77 Mb | Chr 11: 120.35 - 120.36 Mb | |||||||||||
PubMed search | [1] | [2] |
The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to Gs.[1] Stimulation of the receptor results in activation of adenylate cyclase and increased levels of intracellular cAMP. In humans, the glucagon receptor is encoded by the GCGR gene.[2][3]
Glucagon receptors are mainly expressed in liver and in kidney with lesser amounts found in heart, adipose tissue, spleen, thymus, adrenal glands, pancreas, cerebral cortex, and gastrointestinal tract.
Clinical significance
A missense mutation in the GCGR gene is associated with diabetes mellitus type 2.[4]
Inactivating mutation of glucagon receptor in humans causes resistance to glucagon and is associated with pancreatic alpha cell hyperplasia, nesidioblastosis, hyperglucagonemia, and pancreatic neuroendocrine tumors.[5]
References
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Further reading
- Levey GS, Weiss SR, Ruiz E (1975). "Characterization of the glucagon receptor in a pheochromocytoma". J. Clin. Endocrinol. Metab. 40 (4): 720–3. doi:10.1210/jcem-40-4-720. PMID 165216.
- Nakamura S, Rodbell M (1991). "Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes". Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7150–4. doi:10.1073/pnas.88.16.7150. PMC 52251 Freely accessible. PMID 1908089.
- Horuk R, Wright DE (1983). "Partial purification and characterization of the glucagon receptor". FEBS Lett. 155 (2): 213–7. doi:10.1016/0014-5793(82)80605-4. PMID 6303843.
- MacNeil DJ, Occi JL, Hey PJ; et al. (1994). "Cloning and expression of a human glucagon receptor". Biochem. Biophys. Res. Commun. 198 (1): 328–34. doi:10.1006/bbrc.1994.1046. PMID 7507321.
- Fujisawa T, Ikegami H, Yamato E; et al. (1995). "A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus". Diabetologia. 38 (8): 983–5. doi:10.1007/BF00400589. PMID 7589886.
- Unson CG, Macdonald D, Merrifield RB (1993). "The role of histidine-1 in glucagon action". Arch. Biochem. Biophys. 300 (2): 747–50. doi:10.1006/abbi.1993.1103. PMID 8382034.
- Chambers SM, Morris BJ (1996). "Glucagon receptor gene mutation in essential hypertension". Nat. Genet. 12 (2): 122. doi:10.1038/ng0296-122. PMID 8563746.
- Yamato E, Ikegami H, Takekawa K; et al. (1997). "Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1)". Horm. Metab. Res. 29 (2): 56–9. doi:10.1055/s-2007-978985. PMID 9105899.
- Strazzullo P, Iacone R, Siani A; et al. (2001). "Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant". J. Mol. Med. 79 (10): 574–80. doi:10.1007/s001090100257. PMID 11692154.
- Shiota D, Kasamatsu T, Dib SA; et al. (2002). "Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus". Pancreas. 24 (4): 386–90. doi:10.1097/00006676-200205000-00010. PMID 11961492.
- Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241 Freely accessible. PMID 12477932.
- Runge S, Gram C, Brauner-Osborne H; et al. (2003). "Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus". J. Biol. Chem. 278 (30): 28005–10. doi:10.1074/jbc.M301085200. PMID 12724331.
- Hassel S, Eichner A, Yakymovych M; et al. (2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry". Proteomics. 4 (5): 1346–58. doi:10.1002/pmic.200300770. PMID 15188402.
- Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928 Freely accessible. PMID 15489334.
- Mortensen OH, Dichmann DS, Abrahamsen N; et al. (2007). "Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha". Gene. 393 (1-2): 127–36. doi:10.1016/j.gene.2007.01.023. PMID 17374560.
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- ↑ Brubaker PL, Drucker DJ (2002). "Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors". Recept. Channels. 8 (3-4): 179–88. doi:10.1080/10606820213687. PMID 12529935.
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- ↑ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (2009). "Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor". Pancreas. 38 (8): 941–6. doi:10.1097/MPA.0b013e3181b2bb03. PMC 2767399 Freely accessible. PMID 19657311.