Protein kinase C pathway mediates the protective effects of glucagon-like peptide-1 on the apoptosis of islet β-cells

Mol Med Rep. 2015 Nov;12(5):7589-94. doi: 10.3892/mmr.2015.4355. Epub 2015 Sep 24.

Abstract

The incidence of diabetes has been increasing over previous years. It is hypothesized that promoting the survival of islet β-cells is a key direction for the treatment of diabetes. Although gastric bypass surgery improves certain types of diabetes and attenuates its progression, there are certain associated disadvantages (including intestinal obstruction and anastomotic leakage), and quality of life and physical status (such as malnutrition) are significantly affected by gastric bypass surgery. Therefore, it is important to determine the mechanisms underlying the improvement of diabetes by gastric bypass surgery and identify novel gene targets for diabetes therapeutics. In the present study, glucagon‑like peptide‑1 (GLP‑1), whose secretion was markedly increased following gastric bypass surgery, increased the activity of protein kinase C (PKC) in islet β‑cells in a dose‑dependent manner. Additionally, treatment with GLP‑1 boosted cell viability and decreased cell death in starved islet β‑cells, and inhibited mitochondria‑dependent apoptosis by regulating the expression levels of Bcl‑2/Bax. These effects were reversed by inhibiting the PKC pathway using hypericin. Therefore, the present study concluded that GLP‑1 may promote the survival and inhibit the apoptosis of islet β‑cells at least in part by activating the PKC pathway, which is an important underlying mechanism and may be exploited in the treatment of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Survival
  • Enzyme Activation
  • Glucagon-Like Peptide 1 / physiology*
  • Insulin-Secreting Cells / enzymology*
  • Male
  • Mitochondrial Proteins / metabolism
  • Protein Kinase C / metabolism*
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Mitochondrial Proteins
  • Glucagon-Like Peptide 1
  • Protein Kinase C
  • Casp3 protein, rat
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 9