Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets

FEBS Lett. 2002 Feb 27;513(2-3):189-92. doi: 10.1016/s0014-5793(02)02296-2.

Abstract

Elevated islet uncoupling protein-2 (UCP-2) impairs beta-cell function and UCP-2 may be increased in clinical obesity and diabetes. We investigated the effects of glucose and leptin on UCP-2 expression in isolated human islets. Human islets were incubated for 24 h with glucose (5.5-22 mmol/l)+/-leptin (0-10 nmol/l). Some islet batches were incubated at high (22 mmol/l), and subsequently lower (5.5 mmol/l), glucose to assess reversibility of effects. Leptin effects on insulin release were also measured. Glucose dose-dependently increased UCP-2 expression in all islet batches, maximally by three-fold. This was not fully reversed by subsequently reduced glucose levels. Leptin decreased UCP-2 expression by up to 75%, and maximally inhibited insulin release by 47%, at 22 mmol/l glucose. This is the first report of UCP-2 expression in human islets and provides novel evidence of its role in the loss of beta-cell function in diabetes.

MeSH terms

  • Analysis of Variance
  • Cells, Cultured
  • Gene Expression / drug effects*
  • Glucose / pharmacology*
  • Humans
  • Insulin / metabolism
  • Ion Channels
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology
  • Leptin / pharmacology*
  • Membrane Transport Proteins*
  • Mitochondrial Proteins*
  • Protein Biosynthesis*
  • Proteins / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Uncoupling Protein 2

Substances

  • Insulin
  • Ion Channels
  • Leptin
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • RNA, Messenger
  • UCP2 protein, human
  • Uncoupling Protein 2
  • Glucose