Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion.

The effect of a new benzothiadiazine derivative, LN 5330, was studied on insulin secretion from isolated perfused rat pancreas. LN 5330 (1 mg/l to 125mg/l) induced an inhibition of insulin secretion evoked by glucose 1.5 g/l. In all cases the inhibition recorded during the infusion was followed by an increase in insulin secretion after stopping the infusion. This increase was biphasic with LN 5330 at 1, 3, 5 and 15 mg/l. The insulin increase as well as the insulin decrease were dose-related but the additional amount of insulin released after stopping LN 5330 was higher than the amount of insulin which was not released during the infusion of LN 5330. Diazoxide and somatostatin were infused at concentrations which induced an inhibitory effect similar to that obtained with LN 5330 (15 mg/l). When diazoxide infusion was stopped, only a very transient overshoot appeared and after somatostatin infusion insulin secretion progressively returned to reference value. It is concluded that LN 5330 by inducing inhibition and secondary increase of insulin output might be a valuable tool for studying the mechanisms involved in insulin secretion.