Leptin activates ATP‐sensitive potassium channels in the rat insulin‐secreting cell line, CRI‐G1

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Abstract
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. Voltage‐clamp recordings indicate that leptin activates a potassium conductance in the presence of intracellular ATP (5 mm), but has no 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. The leptin‐induced hyperpolarization and increased potassium conductance are completely inhibited by the application of the sulphonylureas tolbutamide (100 μm) and glibenclamide (0.5 μm). Cell‐attached and inside‐out single‐channel recordings indicate that leptin activates tolbutamide‐sensitive KATP channels in CRI‐G1 insulin‐secreting cells.