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

• Published in: FEBS letters Vol. 513; no. 2-3; pp. 189 - 192
• Main Authors: Brown, James E.P, Thomas, Steven, Digby, Janet E, Dunmore, Simon J
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 27.02.2002
• Subjects: Analysis of Variance; Cells, Cultured; Gene expression; Gene Expression - drug effects; Glucose - pharmacology; Glucose toxicity; 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; Type 2 diabetes; Uncoupling Protein 2; β-Cell; Type 2 diabetes; Glucose toxicity; Gene expression; β-Cell
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02296-2

Elevated islet uncoupling protein-2 (UCP-2) impairs β-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 β-cell function in diabetes.