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J Physiol Vol 504, Issue Pt 3 pp 527-535
Copyright © 1997 by The Physiological Society
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Leptin activates ATP-sensitive potassium channels in the rat insulin-secreting cell line, CRI-G1.

J Harvey, F McKenna, P S Herson, D Spanswick and M L Ashford

Department of Biomedical Sciences, University of Aberdeen, UK.

1. Whole-cell current-clamp recordings demonstrate that leptin (0.3-10 nm) hyperpolarizes CRI-G1 insulin-secreting cells. This effect is slow on onset and is not reversed on washout of the leptin. 2. Voltage-clamp recordings indicate that leptin activates a potassium conductance in the presence of intracellular ATP (5 mm), but has not effect in its absence. Following activation of ATP-sensitive K+ (KATP) current by diazoxide (0.2 mm), addition of leptin did not alter cell membrane potential or potassium current further. 3. The leptin-induced hyperpolarization and increased potassium conductance are completely inhibited by the application of the sulphonylureas tolbutamide (100 microM) and glibenclamide (0.5 microM). 4. Cell-attached and inside-out single-channel recordings indicate that leptin activates tolbutamide-sensitive KATP channels in CRI-G1 insulin-secreting cells.







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