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 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.
Harvey
J
J
Department of Biomedical Sciences, University of Aberdeen, UK.
McKenna
F
F
Herson
P S
PS
Spanswick
D
D
Ashford
M L
ML
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002460:Cell Line; D004594:Electrophysiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D020738:Leptin; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D015221:Potassium Channels; D011506:Proteins; D000255:Adenosine Triphosphate; D014044:Tolbutamide