Incretin actions beyond the pancreas: lessons from knockout mice

Curr Opin Pharmacol. 2013 Dec;13(6):946-53. doi: 10.1016/j.coph.2013.09.013. Epub 2013 Oct 4.

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal hormones secreted in response to ingestion of various nutrients. These incretins stimulate insulin secretion from pancreatic β cells in a glucose-dependent fashion. GIP and GLP-1 actions are mediated by specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are expressed in pancreatic β cells and various other tissues and organs. Investigations using mice deficient in GIPR and/or GLP-1R have clarified roles of the incretins in enhancement of glucose-dependent insulin secretion from βcells as well as divergent biological activities with therapeutic implications for diabetes-related complications, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, and comorbidities, such as cognitive impairment, bone fracture and obesity. We review here recent findings on the extra-pancreatic effects of GIP and GLP-1 from the perspective of diabetes treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastric Inhibitory Polypeptide / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Incretins / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Mice, Knockout

Substances

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