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

FEBS Letters
James E P BrownSimon J Dunmore

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.

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Citations

Feb 21, 2006·Antioxidants & Redox Signaling·Gustav Mattiasson, Patrick G Sullivan
Nov 30, 2010·International Journal of Endocrinology·Chunjiong WangJichun Yang
Mar 27, 2012·Journal of Molecular Endocrinology·Laura MarroquíIvan Quesada
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Jul 6, 2010·Life Sciences·Aparajita Dey, Kavitha Swaminathan
Feb 26, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Suresh L Mehta, P Andy Li
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Jan 31, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Carine DuvalLouis Casteilla
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Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman

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