GCGR

Synonyms

GL-R, GCGR, Glucagon Receptor, GGR, Receptors, Glucagon

Description

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.It plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system.

KO Status

In Vitro

Drug Information

Launched drugs: 5
Drugs in clinical trials: 22
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Dasiglucagon

ZP-4207, ZP-GA-1

Approved

Zealand Pharma A/S

Diabetes Mellitus, Type 1, Congenital Hyperinsulinism, Hypoglycemia, Hyperinsulinism

Glucagon (rDNA origin, Lilly)

Approved

Eli Lilly And Company

Diabetes Mellitus, Type 1, Hypoglycemia

Glucagon (rDNA origin, Novo Nordisk)

GL-G

Approved

Novo Nordisk A/S

Hypoglycemia

Glucagon

MP-123456B

Approved

Eli Lilly And Company

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Hypoglycemia, Diabetes Mellitus

Glucagon (Xeris Pharmaceuticals)

Approved

Xeris Pharmaceuticals

Hypoglycemia, Hyperinsulinism

Glucagon intranasal (Eli Lilly/Locemia Solutions)

AMG504-1, LY-900018

Approved

Amg Medical, Locemia Solutions

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Hypoglycemia, Diabetes Mellitus

PRT-001

PRT-001

Phase 3 Clinical

Particle Therapeutics

Hypoglycemia

BI-456906

BI-456906

Phase 2 Clinical

Zealand Pharma A/S

Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Obesity

LGD-6972

LGD-6972, MB-11262, RVT-1502

Phase 2 Clinical

Ligand Pharmaceuticals Inc

Diabetes Mellitus, Type 2

Pegapamodutide

TT-401, OPK-88003, LY-2944876, WG4ID2U7FT

Phase 2 Clinical

Eli Lilly And Company

Diabetes Mellitus, Type 2, Obesity

References

Title

Authors

Source

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Localization of the glucagon receptor gene to human chromosome band 17q25

Menzel S., Stoffel M., Espinosa R. III, Fernald A.A., Le Beau M.M., Bell G.I.,

Genomics 20:327-328(1994)

Role of the glucagon receptor COOH-terminal domain in glucagon-mediated signaling and receptor internalization

Buggy J.J., Heurich R.O., MacDougall M., Kelley K.A., Livingston J.N., Yoo-Warren H., Rossomando A.J.,

Diabetes 46:1400-1405(1997)

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome

Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.,

J. Proteomics 96:253-262(2014)

Conformational dimorphism of self-peptides and molecular mimicry in a disease-associated HLA-B27 subtype

Ruckert C., Fiorillo M.T., Loll B., Moretti R., Biesiadka J., Saenger W., Ziegler A., Sorrentino R., Uchanska-Ziegler B.,

J. Biol. Chem. 281:2306-2316(2006)

Molecular basis for negative regulation of the glucagon receptor

Koth C.M., Murray J.M., Mukund S., Madjidi A., Minn A., Clarke H.J., Wong T., Chiang V., Luis E., Estevez A., Rondon J., Zhang Y., Hotzel I., Allan B.B.,

Proc. Natl. Acad. Sci. U.S.A. 109:14393-14398(2012)

Structure of the human glucagon class B G-protein-coupled receptor

Siu F.Y., He M., de Graaf C., Han G.W., Yang D., Zhang Z., Zhou C., Xu Q., Wacker D., Joseph J.S., Liu W., Lau J., Cherezov V., Katritch V., Wang M.W., Stevens R.C.,

Nature 499:444-449(2013)

Extra-helical binding site of a glucagon receptor antagonist

Jazayeri A., Dore A.S., Lamb D., Krishnamurthy H., Southall S.M., Baig A.H., Bortolato A., Koglin M., Robertson N.J., Errey J.C., Andrews S.P., Teobald I., Brown A.J., Cooke R.M., Weir M., Marshall F.H.,

Nature 533:274-277(2016)

Structure of the full-length glucagon class B G-protein-coupled receptor

Zhang H., Qiao A., Yang D., Yang L., Dai A., de Graaf C., Reedtz-Runge S., Dharmarajan V., Zhang H., Han G.W., Grant T.D., Sierra R.G., Weierstall U., Nelson G., Liu W., Wu Y., Ma L., Cai X., Wu B.,

Nature 546:259-264(2017)

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 38:983-985(1995)

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