Effect of LN 5330 on insulin release and calcium uptake by isolated rat islets of Langerhans. Comparison with diazoxide.

The effect of a new benzothiadiazine derivative, LN 5330, was studied on insulin release and 45Ca++ uptake by isolated rat islets of Langerhans. LN 5330 (0.1 mmol/l) significantly inhibited both insulin release and calcium uptake of islets incubated in MEM (glucose 8.3 mmol/l). This effect was comparable to that of diazoxide. The withdrawal of LN 5330 from the medium resulted in a significant increase of insulin release and calcium uptake by the islets during a subsequent incubation in MEM (glucose 8.3 mmol/l). In contrast, after withdrawal of diazoxide, insulin release and calcium uptake by the islets were not different from the controls. These results suggest a dual action of LN 5330: an effect, similar to that of diazoxide, responsible for the inhibition of insulin release in the presence of the drug; and an effect, specific to LN 5330, which would induce cellular changes, the consequence of which appears only upon withdrawal of the drug.