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⁺]), 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 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.

Key words

Potassium Channel - Lactate - Ca²⁺ Efflux - HIT-T15 Cells - Insulin