A link between endoplasmic reticulum stress-induced β-cell apoptosis and the group VIA Ca2+-independent phospholipase A2 (iPLA2β).

Abstract

Endoplasmic reticulum (ER) stress is becoming recognized as an important contributing factor in various diseases, including diabetes mellitus. Prolonged ER stress can cause β-cell apoptosis; however, the underlying mechanism(s) that contribute to this process are not well understood. Early reports suggested that arachidonic acid metabolites and a Ca(2+)-independent phospholipase A(2) (iPLA(2)) activity play a role in β-cell apoptosis. The PLA(2) family of enzymes catalyse the hydrolysis of the sn-2 substituent (i.e. arachidonic acid) of membrane phospholipids. In light of our findings that the pancreatic islet β-cells are enriched in arachidonate-containing phospholipids and express the group VIA iPLA(2)β, we considered the possibility that iPLA(2)β participates in ER stress-induced β-cell apoptosis. Our work revealed a novel mechanism, involving ceramide generation and triggering of mitochondrial abnormalities, by which iPLA(2)β participates in the β-cell apoptosis process. Here, we review our evidence linking ER stress, β-cell apoptosis and iPLA(2)β. Continued studies in this area will increase our understanding of the contribution of iPLA(2)β to the evolution of diabetes mellitus and will further our knowledge of factors that influence β-cell health in diabetes mellitus and identify potential targets for future therapeutic interventions to prevent β-cell death.

• Authors: X Lei, S Zhang, B Emani, S E Barbour, S Ramanadham
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 12 Suppl 2 Pg. 93-8 (Oct 2010) ISSN: 1463-1326 [Electronic] England
• PMID: 21029305 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: © 2010 Blackwell Publishing Ltd.

Chemical References

• Ceramides
• Group VI Phospholipases A2
• PLA2G6 protein, human
• Calcium

Topics

• Apoptosis (physiology)
• Calcium (metabolism)
• Ceramides (metabolism)
• Diabetes Mellitus, Type 2 (genetics, physiopathology)
• Endoplasmic Reticulum (genetics, physiology)
• Group VI Phospholipases A2 (metabolism, physiology)
• Humans
• Insulin-Secreting Cells (metabolism)
• Mitochondria (physiology)
• Stress, Physiological