HDL inhibits endoplasmic reticulum stress-induced apoptosis of pancreatic β-cells in vitro by activation of Smoothened.

ABSTRACT: Loss of pancreatic β-cell mass and function as a result of sustained ER stress is a core step in the pathogenesis of diabetes mellitus type 2. The complex control of β-cells and insulin production involves hedgehog (Hh) signaling pathways as well as cholesterol-mediated effects. In fact, data from studies in humans and animal models suggest that HDL protects against the development of diabetes through inhibition of ER stress and β-cell apoptosis. We investigated the mechanism by which HDL inhibits ER stress and apoptosis induced by thapsigargin, a sarco/ER Ca²⁺-ATPase inhibitor, in β-cells of a rat insulinoma cell line, INS1e. We further explored effects on the Hh signaling receptor Smoothened (SMO) with pharmacologic agonists and inhibitors. Interference with sterol synthesis o

SUBMITTER: Yalcinkaya M 

PROVIDER: S-EPMC7112150 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature