A radical explanation for glucose-induced beta cell dysfunction

J Clin Invest. 2003 Dec;112(12):1788-90. doi: 10.1172/JCI20501.

Abstract

The development of type 2 diabetes requires impaired beta cell function. Hyperglycemia itself causes further decreases in glucose-stimulated insulin secretion. A new study demonstrates that hyperglycemia-induced mitochondrial superoxide production activates uncoupling protein 2, which decreases the ATP/ADP ratio and thus reduces the insulin-secretory response. These data suggest that pharmacologic inhibition of mitochondrial superoxide overproduction in beta cells exposed to hyperglycemia could prevent a positive feed-forward loop of glucotoxicity that drives impaired glucose tolerance toward frank type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Comment

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Ion Channels
  • Islets of Langerhans / metabolism*
  • Membrane Transport Proteins / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • Models, Biological
  • Pancreatic Diseases / pathology
  • Superoxides / metabolism
  • Uncoupling Protein 2

Substances

  • Blood Glucose
  • Insulin
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • UCP2 protein, human
  • Uncoupling Protein 2
  • Superoxides
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Glucose