Respiratory, ionic, and functional effects of succinate esters in pancreatic islets
Malaisse, W.J.; Rasschaert, J.; Villanueva-Penacarrillo, M.L.; Valverde, I.
American Journal of Physiology 264(3 Pt 1): E428-E433
1993
ISSN/ISBN: 0002-9513 PMID: 8460690 Document Number: 416570
The methyl esters of succinic acid were introduced a few years ago as new potent insulin secretagogues. In the present study, they were found to increase O-2 uptake by rat islets incubated in the absence or presence of D-glucose; to decrease 86Rb outflow from prelabeled islets; to stimulate biosynthetic activity in the islets, with a preferential effect on the synthesis of proinsulin; to inhibit 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca-2+ but to augment 45Ca net uptake and to cause a biphasic stimulation of 45Ca outflow in islets incubated or perifused in the presence of extracellular Ca-2+; and to evoke a biphasic stimulation of insulin release. The insulinotropic action of these methyl esters coincided with a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration, was concentration related in the 2-10 mM range, failed to be duplicated by succinic acid, displayed both Ca-2+ dependency and resistance to a lowering of extracellular pH, and was operative in the absence of D-glucose whether or not the islets were stimulated by nonnutrient secretagogues. It is concluded that the respiratory, cationic, biosynthetic, and secretory responses of the islets to succinate methyl esters display the characteristic features usually encountered in the process of nutrient-stimulated insulin release.