GLP1R

Synonyms

GLP1R, Glucagon-like peptide 1 receptor, Glucagon Like Peptide 1 Receptor, GLP-1 Receptor, GLP-1-R, Seven Transmembrane Helix Receptor, GLP1 Receptor, GLP-1, GLP-1R, Glucagon-Like Peptide-1 Receptor

Description

Glucagon-like peptide 1 receptor is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion.In humans it is synthesised by the gene GLP1R, which is present on chromosome 6.It is a member of the glucagon receptor family of G protein-coupled receptors.GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1,and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1.In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

KO Status

F2 (-/-)

Drug Information

Launched drugs: 12
Drugs in clinical trials: 60
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

PEG-Loxenatide

PEX-168

Approved

Jiangsu Hansoh Pharmaceutical Group Co Ltd

Diabetes Mellitus, Type 2

Beinaglutide

Approved

Second Military Medical University

Diabetes Mellitus, Type 2, Overweight

Liraglutide (Eastern Virginia Medical School)

Eastern Virginia Medical School

Semaglutide oral (Novo Nordisk)

OG-217SC, GLP-1-SNAC, NNC0113-0217, NN-9924

Approved

Novo Nordisk A/S

Diabetes Mellitus, Type 2, Diabetes Mellitus

Insulin glargine/Lixisenatide

HOE-901/AVE-0010

Approved

Sanofi

Diabetes Mellitus, Type 2

Dulaglutide

GLP-1-Fc, LY-2189265

Approved

Eli Lilly And Company

Diabetes Mellitus, Type 2, Metabolic Diseases, Cardiovascular Diseases, Glucose Metabolism Disorders, Diabetes Mellitus

Semaglutide

NN-9535, NNC-0113-0217, NN-9931, NN-9536, 9931

Approved

Novo Nordisk A/S

Diabetes Mellitus, Type 2, Intermittent Claudication, Non-alcoholic Fatty Liver Disease, Kidney Diseases, Liver Diseases, Alzheimer Disease, Obesity, Renal Insufficiency, Chronic, Overweight, Peripheral Arterial Disease, Diabetes Mellitus

Exenatide

Ex-4, AC-2993, LY-2148568, AC-2993-LAR

Approved

Astrazeneca Plc, Eli Lilly And Company

Diabetes Mellitus, Type 2, Renal Insufficiency, Obesity, Diabetes Mellitus

Liraglutide (Jiangsu Chia Tai-Tianqing)

Jiangsu Chia Tai-Tianqing Pharmaceutical Co Ltd, Shanghai Institute Of Pharmaceutical Industry, Lianyungang Runzhong Pharmaceutical Co Ltd

Albiglutide

PGC-GLP-1, GSK-716155

Approved

Glaxosmithkline Plc

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Heart Failure

References


Title

Authors

Source

Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor

Thorens B., Porret A., Buehler L., Deng S., Morel P., Widmann C.,

Diabetes 42:1678-1682(1993)

Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor

Dillon J.S., Tanizawa Y., Wheeler M.B., Leng X., Ligon B.B., Rabin D.U., Yoo-Warren H., Permutt M., Boyd A.E.,

Endocrinology 133:1907-1910(1993)

Cloning and functional expression of a human glucagon-like peptide-1 receptor

Graziano M.P., Hey P.J., Borkowski D., Chicchi G.C., Strader C.D.,

Biochem. Biophys. Res. Commun. 196:141-146(1993)

Signal transduction of the GLP-1-receptor cloned from a human insulinoma

van Eyll B., Lankat-Buttgereit B., Bode H.P., Goeke R., Goeke B.,

FEBS Lett. 348:7-13(1994)

Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences

Wei Y., Mojsov S.,

FEBS Lett. 358:219-224(1995)

The DNA sequence and analysis of human chromosome 6

Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D., Beck S.,

Nature 425:805-811(2003)

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)

Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene

Lankat-Buttgereit B., Goeke B.,

Peptides 18:617-624(1997)

Functional coupling of Cys-226 and Cys-296 in the glucagon-like peptide-1 (GLP-1) receptor indicates a disulfide bond that is close to the activation pocket

Mann R.J., Al-Sabah S., de Maturana R.L., Sinfield J.K., Donnelly D.,

Peptides 31:2289-2293(2010)

Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase

Dezelak M., Bavec A.,

Mol. Biol. Rep. 39:4375-4381(2012)