Uncoupling Protein 2 and Islet Function

  1. Catherine B. Chan1,
  2. Monique C. Saleh1,
  3. Vasilij Koshkin2 and
  4. Michael B. Wheeler2
  1. 1Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Prince Edward, Canada
  2. 2Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada
  1. Address correspondence and reprint requests to Dr. C.B. Chan, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Ave., Charlottetown, PE C1A 4P3 Canada. E-mail: cchan{at}upei.ca

Abstract

Stressors such as chronic hyperglycemia or hyperlipidemia may lead to insufficient insulin secretion in susceptible individuals, contributing to type 2 diabetes. The molecules mediating this effect are just beginning to be identified. Uncoupling protein (UCP)-2 may be one such negative modulator of insulin secretion. Accumulating evidence shows that β-cell UCP2 expression is upregulated by glucolipotoxic conditions and that increased activity of UCP2 decreases insulin secretion. Mitochondrial superoxide has been identified as a posttranslational regulator of UCP2 activity in islets; thus, UCP2 may provide protection to β-cells at one level while simultaneously having detrimental effects on insulin secretion. Interestingly, the latter appears to be the dominant outcome, because UCP2 knockout mice display an increased β-cell mass and retained insulin secretion capacity in the face of glucolipotoxicity.

Footnotes

  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Les Laboratoires Servier.

    • Accepted April 28, 2003.
    • Received March 13, 2003.
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