Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory polypeptide) is a 42-amino-acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extrapancreatic glucoregulatory actions. However, the unfavourable pharmacokinetic profile and the weak biological effects of native GIP limit its effectiveness for the treatment of type 2 diabetes. To overcome this, longer-acting GIP agonists exhibiting enzymatic stability and enhanced bioactivity have been generated and successfully tested in animal models of diabetes. Thus,GIP receptor agonists offer one of the newest classes of potential antidiabetic drug. GIP is also known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or even reverse many of the obesity-associated metabolic disturbances. Strong parallels exist with the beneficial metabolic effects of Roux-en-Y gastric bypass in obese, insulin-resistant humans that surgically ablates GIP-secreting K cells. The purpose of this article is to highlight the therapeutic potential of GIP-based therapeutics in the treatment of type 2 diabetes and obesity. (C) 2009 Elsevier Ltd. All rights reserved.
|Journal||Best Practice and Research: Clinical Endocrinology and Metabolism|
|Publication status||Published - Aug 2009|