Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Physiol Endocrinol Metab. 2012 Dec 1;303(11):E1386-95. doi: 10.1152/ajpendo.00234.2012. Epub 2012 Oct 16.

Role of calcium-independent phospholipase A(2)β in human pancreatic islet β-cell apoptosis.

Author information

  • 1Dept. of Cell, Developmental, and Integrative Biology, Univ. of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract

Death of β-cells due to apoptosis is an important contributor to β-cell dysfunction in both type 1 and type 2 diabetes mellitus. Previously, we described participation of the Group VIA Ca(2+)-independent phospholipase A(2) (iPLA(2)β) in apoptosis of insulinoma cells due to ER stress. To examine whether islet β-cells are similarly susceptible to ER stress and undergo iPLA(2)β-mediated apoptosis, we assessed the ER stress response in human pancreatic islets. Here, we report that the iPLA(2)β protein is expressed predominantly in the β-cells of human islets and that thapsigargin-induced ER stress promotes β-cell apoptosis, as reflected by increases in activated caspase-3 in the β-cells. Furthermore, we demonstrate that ER stress is associated with increases in islet iPLA(2)β message, protein, and activity, iPLA(2)β-dependent induction of neutral sphingomyelinase and ceramide accumulation, and subsequent loss of mitochondrial membrane potential. We also observe that basal activated caspase-3 increases with age, raising the possibility that β-cells in older human subjects have a greater susceptibility to undergo apoptotic cell death. These findings reveal for the first time expression of iPLA(2)β protein in human islet β-cells and that induction of iPLA(2)β during ER stress contributes to human islet β-cell apoptosis. We hypothesize that modulation of iPLA(2)β activity might reduce β-cell apoptosis and this would be beneficial in delaying or preventing β-cell dysfunction associated with diabetes.

PMID:
23074238
[PubMed - indexed for MEDLINE]
PMCID:
PMC3774083
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk