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

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 no effect in its absence. Following activation of ATP-sensitive K+ (K-ATP) 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 mu M) and glibenclamide (0.5 mu M). 4. Cell-attached and inside-out single-channel recordings indicate that leptin activates tolbutamide-sensitive K-ATP channels in CRI-G1 insulin-secreting cells.