Effects of gliquidone on D-glucose metabolism in rat pancreatic islets depend on hexose concentration.
The hypoglycemic sulfonylurea gliquidone, used at a 10 microM concentration, failed to affect the metabolism of D-glucose in rat pancreatic islets incubated 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-14C]glucose oxidation while decreasing the utilization of D-[5-3H]glucose and generation of radioactive acidic metabolites and amino acids from D-[U-14C]glucose. These dissociated effects could conceivably be attributable, respectively, to activation of FAD-linked glycerophosphate dehydrogenase as a result of an increase in cytosolic Ca2+ concentration and to a subsequent inhibition of phosphofructokinase as a result of an increase in cytosolic ATP concentration. The effect of gliquidone on the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was indeed duplicated by repaglinide and suppressed in the absence of extracellular Ca2+ or at low temperature. The present findings thus provide a further illustration of the often contrasting effects of pharmacological and physiological insulinotropic agents on selected metabolic, cationic and functional variables in pancreatic islet cells.
Picton
S
S
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse-Lagae
F
F
Malaisse
W J
WJ
D000818:Animals; D003470:Culture Media; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D003470:Culture Media; D006601:Hexoses; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C010969:gliquidone; D005947:Glucose