THE ESTERS OF CARBOXYLIC NUTRIENTS AS INSULINOTROPIC TOOLS IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

1. In non-insulin-dependent diabetes mellitus, the pancreatic B-cell displays a preferential impairment of its secretory response to D-glucose. 2. A number of agents could be used to restore secretory activity in the diseased B-cell. 3. In this respect, esters of carboxylic nutrients, such as succinic or glutamic acid, present the advantages of stimulating both proinsulin biosynthesis and insulin release, remaining efficient in models of B-cell glucotoxicity, augmenting the secretory response to hypoglycemic pharmacological agents, protecting the B-cell against cytotoxic aggressions, and exerting a long-term beneficial effect upon the secretory potential of the endocrine pancreas. 4. Potential limitations of this new therapeutical approach, such as the generation of methanol from the esters, their postulated inefficacy after enteral administration, or the occurrence of extrapancreatic metabolic effects may be circumvented. 5. The esters of carboxylic nutrients could even be used in other cells endangered by ATP depletion.