New insight into the mechanisms underlying the function of the incretin hormone glucagon-like peptide-1 in pancreatic β-cells: the involvement of the Wnt signaling pathway effector β-catenin

Islets. 2012 Nov-Dec;4(6):359-65. doi: 10.4161/isl.23345. Epub 2012 Nov 1.

Abstract

During the past two decades, the exploration of function of two incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), has led to the development of two categories of novel therapeutic agents for diabetes and its complications, known as GLP-1 receptor (GLP-1R) agonists and DPP-IV inhibitors. Mechanisms underlying the function of GLP-1, however, still need to be further explored. GLP-1 not only functions as an incretin hormone in stimulating insulin secretion in response to nutritional, hormonal and neuronal stimulations, but also acts as an "insulin-like" factor in β-cell and extra-pancreatic organs. In addition to these insulinotropic and insulinomimetic effects, GLP-1 was shown to exert its protective effect in β-cell by repressing the expression of TxNIP, a mediator of glucolipotoxicity. A number of recent studies have shown that the Wnt signaling pathway effector, the bipartite transcription factor β-catenin/TCF, controls not only the production of GLP-1, but also the function of GLP-1. Furthermore, previously assumed "degradation" products of GLP-1(7-36)amide, including GLP-1(9-36)amide and GLP-1(28-36)amide, have been shown to exert beneficial effect in pancreas and extra-pancreatic tissues or cell lineages. Here we summarized our current knowledge on the metabolic, proliferative and protective effects of GLP-1(7-36)amide and its cleavage fragments, mainly focusing on pancreatic β-cells and the involvement of the Wnt signaling pathway effector β-catenin.

Keywords: GLP-1; TCF7L2; TxNIP; Wnt signaling pathway; β-catenin.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism*

Substances

  • beta Catenin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1