Impairment of insulin release by methylation inhibitors

Abstract The possible participation of enzymatic methylation reactions in the process of insulin release was investigated in rat pancreatic islets. The combination of 3-deazaadenosine and dl -homocysteine impaired the incorporation of 3 H-methyl from l -[methyl- 3 H]methionine into endogenous islet proteins and phospholipids, but failed to affect turnover in the phosphatidylinositol cycle. The inhibitors of methylation decreased insulin release evoked by d -glucose or the combinations of d -glucose and gliclazide, l -leucine and l -glutamine, or Ba 2+ and theophylline. The inhibitors of methylation did not impair either the oxidation of d -glucose or affect its capacity to decrease K + conductance, stimulate Ca 2+ inflow and provoke 45 Ca accumulation in pancreatic islets. It is proposed that, in the process of insulin secretion, a methyl acceptor protein and/or phospholipid play(s) a limited modulatory role in the coupling of cytosolic Ca 2+ accumulation to exocytosis.