The role of G protein-coupled receptor 40 in lipoapoptosis in mouse beta-cell line NIT-1

J Mol Endocrinol. 2007 Jun;38(6):651-61. doi: 10.1677/JME-06-0048.

Abstract

Free fatty acids (FFAs) exert divergent effects on beta-cells. Acute exposure to FFAs stimulates insulin secretion, whereas chronic exposure impairs beta-cell function and induces apoptosis. The G protein-coupled receptor 40 (GPR40) is preferentially expressed in beta-cells and is activated by a wide range of FFAs. In this study, we used small interfering RNA technology and apoptosis assay in mouse beta-cell NIT-1 to address the role of GPR40 in beta-cell lipoapoptosis and function. Results showed that palmitate induced beta-cell apoptosis, which was not mediated through GPR40, whereas oleate protected NIT-1 cells from palmitate-induced lipoapoptosis, which was mediated at least in part through GPR40. Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and MAP kinase (MAPK) pathways, we found that oleate promoted the activation of extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40, increased the expression of early growth response gene-1, leading to the anti-lipoapoptotic effect on NIT-1 cells. It was suggested that GPR40 might be implicated in the control of beta-cell mass plasticity and GPR40 probably provide a link between obesity and type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Fatty Acids, Nonesterified / physiology*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Mice, Inbred NOD
  • Obesity / metabolism
  • Obesity / pathology
  • RNA Interference
  • RNA, Small Interfering / physiology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*

Substances

  • Fatty Acids, Nonesterified
  • Ffar1 protein, mouse
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled