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 K-Ca channels, while 100 nmol/l glibenclamide had no effect on K-Ca channels, but blocked K-ATP channels. Lactate at a concentration of 10 mmol/l activated both the K-ATP and K-Ca 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 Ca-45(2+) 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.