Effects of gliquidone on D-glucose metabolism in rat pancreatic islets depend on hexose concentration

The hypoglycemic sulfonylurea gliquidone, used at a 10 mu M concentration, failed to affect the metabolism of D-glucose in rat pancreatic islets incub ated in the presence of 5.6 mM, 8.3 mM or 16.7 mM D-glucose. However, at 2. 8 mM D-glucose, gliquidone increased D-[U-C-14]glucose oxidation while decr easing the utilization of D-[5-H-3]glucose and generation of radioactive ac idic metabolites and amino acids from D-[U-C-14]glucose. These dissociated effects could conceivably be attributable, respectively, to activation of F AD-linked glycerophosphate dehydrogenase as a result of an increase in cyto solic Ca2+ concentration and to a subsequent inhibition of phosphofructokin ase as a result of an increase in cytosolic ATP concentration. The effect o f gliquidone on the paired ratio between D-[U-C-14]glucose oxidation and D- [5-H-3]glucose utilization was indeed duplicated by repaglinide and suppres sed in the absence of extracellular Ca2+ or at low temperature. The present findings thus provide a further illustration of the often contrasting effe cts of pharmacological and physiological insulinotropic agents on selected metabolic, cationic and functional variables in pancreatic islet cells.