Insulinotropic action of 1,2,3-Tri(methylsuccinyl)glycerol ester.

A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol ester (3SMG), was found to stimulate insulin release from rat pancreatic islets. In the presence of 7 mM d-glucose, a 10 microM concentration of 3SMG was sufficient to cause a significant increase in insulin output. The ester mimicked the effect of other nutrient secretagogues in enhancing the synthesis of islet peptides, with a preferential action on proinsulin as distinct from nonhormonal peptides, in decreasing 86Rb outflow from prelabeled islets, and in stimulating Ca2+ inflow into the islet cells. It is proposed, therefore, that 3SMG displays the attributes suitable for stimulation or potentiation of insulin release in noninsulin-dependent diabetes, without requiring administration in large amounts and, hence, without the risk of excessive hepatic gluconeogenesis.