Uncoupling protein 2 and islet function

Diabetes. 2004 Feb;53 Suppl 1:S136-42. doi: 10.2337/diabetes.53.2007.s136.

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 beta-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 beta-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 beta-cell mass and retained insulin secretion capacity in the face of glucolipotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Gene Expression Regulation / physiology
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Ion Channels
  • Islets of Langerhans / physiology*
  • Membrane Transport Proteins / physiology*
  • Mitochondrial Proteins / physiology*
  • Nutritional Physiological Phenomena
  • Reactive Oxygen Species / metabolism
  • Uncoupling Protein 2

Substances

  • Insulin
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • UCP2 protein, human
  • Ucp2 protein, mouse
  • Uncoupling Protein 2