Available structures
PDBOrtholog search: PDBe RCSB
AliasesGCGR, GGR, GL-R, glucagon receptor, MVAH
External IDsOMIM: 138033 MGI: 99572 HomoloGene: 131 GeneCards: GCGR
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 17: 81.8 – 81.81 MbChr 11: 120.42 – 120.43 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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 G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the activation of adenylate cyclase and phospholipase C and in increased levels of the secondary messengers intracellular cAMP and calcium. In humans, the glucagon receptor is encoded by the GCGR gene.

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.

Signal transduction pathway

A glucagon receptor, upon binding with the signaling molecule glucagon, initiates a signal transduction pathway that begins with the activation of adenylate cyclase, which in turn produces cyclic AMP (cAMP). Protein kinase A, whose activation is dependent on the increased levels of cAMP, is responsible for the ensuing cellular response in the form of protein kinase 1 and 2. The ligand-bound glucagon receptor can also initiate a concurrent signaling pathway that is independent of cAMP by activating phospholipase C. Phospholipase C produces DAG and IP3 from PIP2, a phospholipid phospholipase C cleaves off of the plasma membrane. Ca2+ stores inside the cell release Ca2+ when its calcium channels are bound by IP3.[5][6]


glucagon/glucagon receptor (blue) with glucagon bound (pink)

The 3D crystallographic structures of the seven transmembrane helical domain (7TM)[7] and the extracellular domain (ECD)[8] and an electron microscopy (EM) map of full length glucagon receptor[9] have been determined. Furthermore, the structural dynamics of an active state complex of the Glucagon receptor, Glucagon, the Receptor activity-modifying protein, and the G-protein C-terminus has been determined using a computational and experimental approach.[10]

Clinical significance

A missense mutation at 17q25[11] in the GCGR gene is associated with diabetes mellitus type 2.[12]

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, also known as Mahvash disease.[13][14]


  1. ^ a b c ENSG00000288269 GRCh38: Ensembl release 89: ENSG00000215644, ENSG00000288269 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025127 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Urry LA, Cain ML, Wasserman SA, Minorsky PV, Reece JB, Campbell NA. Campbell biology (Eleventh ed.). New York, NY. ISBN 0-13-409341-0. OCLC 956379308.
  6. ^ Scanes CG (30 June 2014). Sturkie's avian physiology (Sixth ed.). London, England. ISBN 978-0-12-407243-5. OCLC 884590323.((cite book)): CS1 maint: location missing publisher (link)
  7. ^ PDB: 4L6R​; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, Liu W, Lau J, Cherezov V, Katritch V, Wang MW, Stevens RC (Jul 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature. 499 (7459): 444–9. Bibcode:2013Natur.499..444S. doi:10.1038/nature12393. PMC 3820480. PMID 23863937.
  8. ^ PDB: 4ERS​; Koth CM, Murray JM, Mukund S, Madjidi A, Minn A, Clarke HJ, Wong T, Chiang V, Luis E, Estevez A, Rondon J, Zhang Y, Hötzel I, Allan BB (Sep 2012). "Molecular basis for negative regulation of the glucagon receptor". Proceedings of the National Academy of Sciences of the United States of America. 109 (36): 14393–8. Bibcode:2012PNAS..10914393K. doi:10.1073/pnas.1206734109. PMC 3437825. PMID 22908259.
  9. ^ Yang L, Yang D, de Graaf C, Moeller A, West GM, Dharmarajan V, Wang C, Siu FY, Song G, Reedtz-Runge S, Pascal BD, Wu B, Potter CS, Zhou H, Griffin PR, Carragher B, Yang H, Wang MW, Stevens RC, Jiang H (July 2015). "Conformational states of the full-length glucagon receptor". Nature Communications. 6: 7859. Bibcode:2015NatCo...6.7859Y. doi:10.1038/ncomms8859. PMC 4532856. PMID 26227798.
  10. ^ Weston C, Winfield I, Harris M, Hodgson R, Shah A, Dowell SJ, Mobarec JC, Woodcock DA, Reynolds CA, Poyner DR, Watkins HA, Ladds G (August 2016). "Receptor activity modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors receptor". The Journal of Biological Chemistry. 291 (42): 21925–21944. doi:10.1074/jbc.M116.751362. PMC 5063977. PMID 27566546.
  11. ^ 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". Receptors & Channels. 8 (3–4): 179–88. doi:10.1080/10606820213687. PMID 12529935.
  12. ^ Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C (Mar 1995). "A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus". Nature Genetics. 9 (3): 299–304. doi:10.1038/ng0395-299. PMID 7773293. S2CID 26951878.
  13. ^ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (Nov 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. PMID 19657311.
  14. ^ Yu R (2018). "Mahvash Disease: 10 Years After Discovery". Pancreas. 47 (5): 511–15. doi:10.1097/MPA.0000000000001044. PMID 29702528. S2CID 13871451.

Further reading