METABOLIC EFFECTS AND FATE OF SUCCINATE ESTERS IN PANCREATIC-ISLETS

The metabolic effects and the catabolism of succinate methyl esters were examined in rat pancreatic islets. The esters augmented (CO2)-C-14 production from islets prelabeled with L-[U-C-14]glutamine but inhibited NH4+ output, suggesting that they do not activate glutamate dehydrogenase. They decreased (CO2)-C-14 output from islets prelabeled with [U-C-14]palMitate. They had little effect on the oxidation of exogenoUS D-[3,4-C-14]glucose, D-[2-C-14]glucose, D-[6-C-14]glucose, or D-[1-C-14]glucose, suggesting unaltered ratio between the input of acetyl residues and four- or five-carbon metabolites, such as succinate, into the Krebs cycle. By following the fate of both [1,4-C-14]succinate dimethyl ester and [2,3-C-14]succinate dimethyl ester, data were obtained to indicate that succinate is efficiently formed from the ester and further metabolized, leading to the generation of C-14-labeled acidic metabolites including pyruvate and L-lactic acid, CO2, and amino acids. It is proposed that a concerted increase of both succinate and acetyl residue influx into the Krebs cycle accounts for the increase in 02 uptake caused by the succinate methyl esters and, hence, for stimulation of both proinsulin biosynthesis and insulin release.