UCP2 is Highly Expressed in Pancreatic Alpha-cells and Influences Secretion and Survival

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Aug 15

PMID 18701716

Citations 37

Authors

Jingyu Diao

Emma M Allister

Vasilij Koshkin

Simon C Lee

Alpana Bhattacharjee

Christine Tang

Adria Giacca

Catherine B Chan

Michael B Wheeler

Affiliations

Soon will be listed here.

Abstract

In pancreatic beta-cells, uncoupling protein 2 (UCP2) influences mitochondrial oxidative phosphorylation and insulin secretion. Here, we show that alpha-cells express significantly higher levels of UCP2 than do beta-cells. Greater mitochondrial UCP2-related uncoupling was observed in alpha-cells compared with beta-cells and was accompanied by a lower oxidative phosphorylation efficiency (ATP/O). Conversely, reducing UCP2 activity in alpha-cells was associated with higher mitochondrial membrane potential generated by glucose oxidation and with increased ATP synthesis, indicating more efficient metabolic coupling. In vitro, the suppression of UCP2 activity led to reduced glucagon secretion in response to low glucose; however, in vivo, fasting glucagon levels were normal in UCP2(-/-) mice. In addition to its effects on secretion, UCP2 played a cytoprotective role in islets, with UCP2(-/-) alpha-cells being more sensitive to specific death stimuli. In summary, we demonstrate a direct role for UCP2 in maintaining alpha-cell function at the level of glucose metabolism, glucagon secretion, and cytoprotection.

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