G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes

Pharmacol Ther. 2007 Dec;116(3):437-48. doi: 10.1016/j.pharmthera.2007.08.002. Epub 2007 Aug 29.


Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G protein)-coupled receptors (GPCR). Examples of islet GPCR are GPR40 and GPR119, which are GPCR with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors acetylcholine (ACh; M(3) muscarinic receptors) and noradrenaline (beta(2)- and alpha(2)-adrenoceptors) and for the neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP; PAC(1) and VPAC(2) receptors), cholecystokinin (CCK(A) receptors) and neuropeptide Y (NPY Y1 receptors). Other islet GPCR are the cannabinoid receptor (CB(1) receptors), the vasopressin receptors (V1(B) receptors) and the purinergic receptors (P(2Y) receptors). The islet GPCR couple mainly to adenylate cyclase and to phospholipase C (PLC). Since important pharmacological strategies for treatment of type 2 diabetes are stimulation of insulin secretion and inhibition of glucagon secretion, islet GPCR are potential drug targets. This review summarizes knowledge on islet GPCR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / physiology*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Gastrointestinal Hormone / physiology
  • Receptors, Glucagon / physiology
  • Receptors, Neurotransmitter / physiology
  • Signal Transduction


  • FFAR1 protein, human
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Receptors, G-Protein-Coupled
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Receptors, Neurotransmitter
  • gastric inhibitory polypeptide receptor