Lactate production in pancreatic islets.
Lactate production, glucose utilization, glucose oxidation, and insulin release were studied in islets from rat and ob/ob mice. Lactate was determined with a highly sensitive method, based on esterification, subsequent separation, and quantitation with high-performance liquid chromatography. There was a significant lactate production in the absence of glucose, which increased with glucose concentrations up to 3 mmol/l, reaching its half-maximal rate in the presence of 0.2-1.0 mmol/l glucose in both species. Glucose utilization displayed a wider glucose concentration dependence, with a K0.5 value between 3 and 10 mmol/l glucose. The rates of glucose utilization and lactate production were similar at 3 mmol/l glucose in rat islets and at about 6 mmol/l glucose in ob/ob mice islets. Saturation of lactate production at low glucose concentrations is probably contributing to the observed preferential stimulation of oxidative metabolism at higher concentrations. D-Mannoheptulose caused a marked inhibition of glucose utilization and glucose oxidation at 20 mmol/l glucose in islets from rat or ob/ob mice, as would be expected from a competitive inhibition of glucokinase. By contrast, D-mannoheptulose reduced only marginally the islet metabolism at 3 mmol/l glucose, which is consistent with an effective mannoheptulose-induced inhibition of the glucokinase-dependent, minor part of glucose phosphorylation at this low glucose concentration.
Tamarit-Rodriguez
J
J
Department of Biochemistry, School of Medicine, Complutense University, Madrid, Spain. tamarit@eucmax.sim.ucm.es
Idahl
L A
LA
Giné
E
E
Alcazar
O
O
Sehlin
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D009765:Obesity / Q000235:genetics; D009994:Osmolar Concentration; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D019344:Lactic Acid; D008356:Mannoheptulose; D005947:Glucose