Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Alcohol. 2012 Feb;46(1):89-99. doi: 10.1016/j.alcohol.2011.04.001. Epub 2011 Aug 12.

Ethanol causes endoplasmic reticulum stress and impairment of insulin secretion in pancreatic β-cells.

Author information

  • 1Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

Chronic ethanol consumption increases the risk of type 2 diabetes mellitus, and ethanol has been reported to cause insulin resistance and, inconsistently, to reduce insulin secretion. The mechanism(s) underlying the reduction of insulin secretion by ethanol is not known. We used β-cell lines and isolated murine islets to determine the effect of ethanol on insulin content and secretion at low- and high-glucose concentrations, in the presence of KCl, diazoxide, tolbutamide, and regulators of cyclic AMP and protein kinase C (PKC). We also determined the gene expression of insulin; pancreas duodenum homeobox 1; and endoplasmic reticulum (ER) stress markers, such as Chop, ERp57, glucose-regulated protein 78/binding immunoglobulin protein, and inositol 1,4,5-triphosphate receptors. Ethanol reduced insulin secretion by interfering with muscarinic signaling and PKC activation but not the K-ATP channels. In addition, ethanol reduced insulin content and caused ER stress. The deleterious effects of ethanol on β-cells were prevented by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase, suggesting that ethanol metabolism is required for these effects.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
21840159
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk