Inhibition by kynurenine metabolites of proinsulin synthesis in isolated pancreatic islets

The effect of kynurenine metabolites on insulin biosynthesis was investigated in isolated pancreatic islets of the rat. Both quinaldic acid and 8-hydroxyquinaldic acid were found to produce significant inhibition of the proinsulin synthesis. However, the conversion process of proinsulin to insulin in the islet was not affected by these kynurenine metabolites. Furthermore, the inhibitory effect of these end-metabolites of kynurenine was characterized by preferential inhibition of proinsulin synthesis as distinct from non-insulin protein synthesis in the islet. In contrast to the significant inhibitory effect of quinaldic acid and 8-hydroxyquinaldic acid on proinsulin synthesis, xanthurenic acid and kynurenic acid were far less effective, and L-tryptophan, L-kynurenine, 3-hydroxyanthranilic acid and quinolinic acid showed little ability to inhibit proinsulin synthesis in islets.