EFFECTS OF GLYCEROL-1,2-DIMETHYLSUCCINATE AND PROPANEDIOL-1,2-DIMETHYLSUCCINATE ON INSULIN RELEASE AND PROTEIN-BIOSYNTHESIS IN ISLETS OF GOTO-KAKIZAKI RATS

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependen t diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of t wo of these novel esters, namely glycerol-l,2-dimethylsuccinate (2.5 m M) and propanediol-1,2-dimethylsuccinate (1.0 mM), upon the release of insulin and the de novo biosynthesis of peptides in islets from hered itarily diabetic Goto-Kakizaki rats. Whereas D-glucose (2.8 to 16.7 mM ) caused a concentration-related stimulation of insulin release in the islets of the diabetic rats, the two esters of succinic acid only inc reased modestly, and often not significantly, insulin secretion. Never theless, they both markedly increased the incorporation of L-[4-H-3]ph enylalanine into trichloroacetic acid-precipitable material in islets deprived of any other exogenous nutrient. These findings indicate that , at variance with all pharmaceutical agents presently used or propose d as insulin secretagogues in the treatment of type 2 diabetes, glycer ol-l,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate, consid ered as islet cell nutrients, display, in addition to their insulinotr opic action, the property of stimulating biosynthetic activity in the endocrine pancreas of animals affected by this disease.