Genetic variants affecting incretin sensitivity and incretin secretion

Diabetologia. 2010 Nov;53(11):2289-97. doi: 10.1007/s00125-010-1876-8. Epub 2010 Aug 17.


Recent genome-wide association studies identified several novel risk genes for type 2 diabetes. The majority of these type 2 diabetes risk variants confer impaired pancreatic beta cell function. Though the molecular mechanisms by which common genetic variation within these loci affects beta cell function are not completely understood, risk variants may alter glucose-stimulated insulin secretion, proinsulin conversion, and incretin signals. In humans, the incretin effect is mediated by the secretion and insulinotropic action of two peptide hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. This review article aims to give an overview of the type 2 diabetes risk loci that were found to associate with incretin secretion or incretin action, paying special attention to the potential underlying mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Gastric Inhibitory Polypeptide / metabolism
  • Genome-Wide Association Study
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Incretins / metabolism*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology


  • Incretins
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1