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 14CO2 production from islets prelabeled with L-[U-14C]-glutamine but inhibited NH4+ output, suggesting that they do not activate glutamate dehydrogenase. They decreased 14CO2 output from islets prelabeled with [U-14C]palmitate. They had little effect on the oxidation of exogenous D-[3,4-14C]glucose, D-[2-14C]glucose, D-[6-14C]glucose, or D-[1-14C]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 [1,4-14C]succinate dimethyl ester and [2,3-14C]succinate dimethyl ester, data were obtained to indicate that succinate is efficiently formed from the ester and further metabolized, leading to the generation of 14C-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 O2 uptake caused by the succinate methyl esters and, hence, for stimulation of both pro-insulin biosynthesis and insulin release.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Sener
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D010100:Oxygen / Q000493:pharmacokinetics; D010101:Oxygen Consumption / Q000502:physiology; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D013386:Succinates / Q000378:metabolism*
D002250:Carbon Radioisotopes; D004952:Esters; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D013386:Succinates; D000641:Ammonia; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen