EFFECTS OF A NEW CALMODULIN INHIBITOR (W-7) ON GLUCOSE-INDUCED INSULIN RELEASE AND BIOSYNTHESIS

Abstract

The effects of a new calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-naphthalene-sulfonamide (W-7) on glucose-induced insulin release and biosynthesis were studied using isolated islets from rat pancreas. Insulin release stimulated by 10 or 20 mM glucose was inhibited by the addition of W-7 (25-200 .mu.M). The maximal inhibition by W-7 (.apprx. 30%) was smaller than that by trifluoperazine (.apprx. 75%). The basal release of insulin in the presence of a substimulating concentration of glucose (2.8 mM) was not modified by W-7. W-7 affected neither the rate of glucose oxidation in the islets nor the total incorporation of [3H]Leu into the proinsulin and insulin fractions. The radioactivity of [3H]Leu incorporated into the insulin fractions was decreased by W-7. A Ca2+-calmodulin related mechanism apparently is involved in glucose-induced insulin release and the conversion of proinsulin to insulin.