Activation of GPR40 attenuates chronic inflammation induced impact on pancreatic β-cells health and function.

ABSTRACT:

Background

Chronic inflammation-mediated β-cell apoptosis is known to decrease β-cell mass in diabetes leading to reduced insulin secretion. Exposure to pro-inflammatory cytokines can stimulate apoptosis in pancreatic β-cells. The G protein coupled receptor 40 (GPR40) is implicated for glucose induced insulin secretion. We hypothesized that GPR40 activation can protect β-cells from inflammation-induced apoptosis and restore glucose stimulated insulin secretion.

Results

By exposing NIT1 insulinoma cells and rat islets to a cocktail of pro-inflammatory cytokines (TNFα and IL1β), we mimicked inflammatory signaling as seen by JNK and NFκB activation and increased mRNA levels of TNFα, IL1β and NOS2a. These changes were reversed by pharmacological activation of GPR40 by a specific

SUBMITTER: Verma MK 

PROVIDER: S-EPMC4083038 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature