Glucagon-like peptide 1 receptor

3C59, 3C5T, 3IOL, 4ZGM274014652ENSG00000112164ENSMUSG00000024027P43220O35659NM_002062NM_021332NP_002053NP_067307The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas. 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. The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas. 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. GLP1R binds glucagon-like peptide-1 (GLP1) and glucagon as its natural endogenous agonists. Receptor agonists: Receptor antagonists: Receptor positive allosteric modulators: GLP1R is known to be expressed in pancreatic beta cells. Activated GLP1R stimulates the adenylyl cyclase pathway which results in increased insulin synthesis and release of insulin. Consequently, GLP1R has been a target for developing drugs usually referred to as GLP1R agonists to treat diabetes mellitus. Exendin-4 is one of the peptides used therapeutically to treat diabetes, and its biological binding mode to the GLP-1R has been demonstrated using genetically engineered amino acids. GLP1R is also expressed in the brain where it is involved in the control of appetite. Furthermore, mice that over express GLP1R display improved memory and learning. Stretch responsive vagal neurons in the stomach and intestines also express GLP1R. GLP1R neurons particularly and densely innervate stomach muscle and can communicate with additional organ systems changing breathing and heart rate due to activation. The diabetic, pancreatic, and neuroprotection implications of GLP1R are also thought to be potential therapies for treating the diabetes and energy metabolism abnormalities associated with Huntington's disease affecting the brain and periphery. Exendin-4, an FDA-approved antidiabetic glucagon-like peptide 1 (GLP-1) receptor agonist, has been tested in mice with the mutated human huntingtin protein showing neurodegenerative changes, motor dysfunction, poor energy metabolism, and high blood glucose levels. Exendin-4 (Ex-4) treatment reduced the accumulation of mutated human huntingtin protein aggregates, improved motor function, extended the survival time, improved glucose regulation, and decreased brain and pancreas pathology.