Therapeutic potential for GIP receptor agonists and antagonists.
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.
Irwin
Nigel
N
School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, Northern Ireland, UK. n.irwin@ulster.ac.uk
Flatt
Peter R
PR
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism; D015390:Gastric Bypass; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*
D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D018819:Dipeptidyl Peptidase 4