Influence of anoxia on glucose metabolism in pancreatic islets: lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux

Abstract

When equilibrated with O2-CO2 (95:5), pancreatic islets of non-inbred ob/ob-mice exhibited a sigmoidal dependence of 3H2O production on D-(5-3H)-glucose concentration; the rate was most sensitive to changes of glucose concentration around 5mM and tended to be maximum above about 15mM glucose. 3H2O production from more than 5 mM D-(5-3H)-glucose was about twice as fast as the production of 14CO2 from equimolar D-(U-14C)-glucose. Islets equilibrated with N2-CO2 (95:5) did not exhibit a sigmoidal dose-response curve for 3h2o production, the process being inhibited by anoxia at glucose concentrations above 5mM. Pieces of exocrine pancreas had a slower aerobic 3H2O production than the islets and showed a clear enhancement of the process during anoxia. In comparison with oxygenated islets, anoxic islets exhibited decreased concentrations of glucose-6-phosphate and increased concentrations of furctose-1,6-diphosphate. The concomitant inhibition of glycolytic flux may be due to a low lactate dehydrogenase activity in islets yielding a slow reoxidation of NADH and a slow phosphoglyceraldehyde oxidation under anaerobic conditions.