Effect of repaglinide upon nutrient metabolism, biosynthetic activity, cationic fluxes and insulin release in rat pancreatic islets

摘要: This study aims at gaining further insight into the mode of action repaglinide in pancreatic islet B-cells. At a 1.0 mumol/L concentration, meglitinide analog failed to affect metabolism exogenous D-glucose and that endogenous nutrients islets prelabeled with either L-[U-14C]glutamine or [U-14C]palmitate. Likewise, (1.0 mumol/L) modify significantly incorporation L-[4-3H]phenylalanine TCA-precipitable material exposed close-to-physiological concentration (7.0 mmol/L). The threshold for insulinotropic was close 0.1-1.0 maximal response reached 10.0 incubated presence 5.6-8.3 mmol/L D-glucose. higher hexose (16.7 mmol/L), however, an enhancing (10 upon glucose-stimulated insulin release only observed over 25 min stimulation perifused islets, no significant increase output being detected when were (0.1 0.1 mmol/L) 90 incubation high level. evoked by 16.7 coincided modest 86Rb outflow marked 45Ca efflux from suggesting Ca2+ influx cells subsequent activation Ca(2+)-responsive K+ channels. When administration halted, reversibility its cationic secretory effects more pronounced rather than low (6.0 concentration. These findings support view primary site consists remodeling fluxes, document this drug displays favorable attributes as agent treatment non-insulin-dependent diabetes, such lack interference nutrient biosynthetic activity isolated insulin-releasing capacity augment, least transiently,