Lactate stimulates insulin secretion without blocking the K+ channels in HIT-T15 insulinoma cells.
To clarify the mechanism by which lactate affects insulin secretion, we investigated the effect of lactate on insulin secretion, cytosolic free Ca2+ ([Ca2+](i), the ATP sensitive K+ channel (K(ATP)) and the Ca2+-activated K+ channel (K(Ca)) in HIT-T15 cells, and the results were compared with those of glucose and glibenclamide. All three agents caused insulin secretion and increased [Ca2+](i), but the effects on the K+ channels were different. In cell-attached patch configurations, 10 mmol/l glucose blocked both the K(ATP) and KCa channels, while 100 nmol/l glibenclamide had no effect on KCa channels, but blocked K(ATP) channels. Lactate at a concentration of 10 mmol/l activated both the K(ATP) and KCa channels, not only in cell-attached, but also in inside-out patch configurations, indicating that the increase in [Ca2+](i) and secretion of insulin by lactate cannot be explained by the blocking of the K+ channels. Lactate, at concentrations of 10 mmol/l and 50 mmol/l decreased 45Ca2+ efflux, while glibenclamide increased the efflux. These results suggest that the lactate-induced Ca2+ increase is not due to the closing of K+ channels, but at least in part, to the suppression of Ca2+ efflux from HIT cells.
Akiyoshi
H
H
Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima City, Japan.
Iwamoto
M
M
Nakaya
Y
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000503:physiopathology*; D019344:Lactic Acid / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D002132:Calcium Radioisotopes; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D005905:Glyburide; D002118:Calcium