INSULINOTROPIC ACTION OF 1,2,3-TRI(METHYLSUCCINYL)GLYCEROL ESTER

A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol este r (3SMG), was found to stimulate insulin release from rat pancreatic i slets. In the presence of 7 mM D-glucose, a 10 mu M concentration of 3 SMG was sufficient to cause a significant increase in insulin output. The ester mimicked the effect of other nutrient secretagogues in enhan cing the synthesis of islet peptides, with a preferential action on pr oinsulin as distinct from nonhormonal peptides, in decreasing Rb-86 ou tflow from prelabeled islets, and in stimulating Ca2+ inflow into the islet cells. It is proposed, therefore, that 3SMG displays the attribu tes suitable for stimulation or potentiation of insulin release in non insulin-dependent diabetes, without requiring administration in large amounts and, hence, without the risk of excessive hepatic gluconeogene sis. (C) 1997 Academic Press.