Stimulation of insulin release and biosynthetic activity by 1,2,3-tri(methylsuccinyl)glycerol ester in pancreatic islets of Goto-Kakizaki rats

A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol ester (3SMG) caused a concentration-related stimulation of insulin release evoked by 7.0 mM D-glucose in islets from hereditarily diabetic Goto-Kakizaki rats. At the same hexose concentration, as little as 0.1 mM 3SMG was sufficient to augment insulin secretion to the same rate as that otherwise caused by a close-to-maximal concentration of D-glucose (16.7 mM). Likewise, 3SMG stimulated the incorporation of L-[4-H-3]phenylalanine (3.4 mu M) into TCA-precipitable material in the islets from the diabetic animals. Even in the absence of any other exogenous nutrient, 2.5 mM 3SMG augmented biosynthetic activity above the basal value, to a level not lower than that recorded in the sole presence of 16.7 mM D-glucose. These findings indicate that this novel ester displays suitable attributes as a potential insulinotropic agent in the treatment of non-insulin-dependent diabetes mellitus.