Hexose metabolism in pancreatic islets. Feedback control of d-glucose oxidation by functional events

Abstract

A rise in extracellular d-glucose concentration in pancreatic islet cells causes a greater relative increase in the oxidation of pyruvate and acetyl residues than in glycolysis. A possible explanation for such an unusual situation was sought in the present study. The preferential stimulation of mitochondrial oxidative events was found to display a sigmoidal dependency on hexose concentration, and an exponential time course during prolonged exposure of the islets to a high concentration of d-glucose. The preferential stimulation of mitochondrial oxidative events was abolished in islets incubated in the presence of cycloheximide and absence of Ca 2+, in which case the oxidation of d-[6- 14C]glucose was more severely inhibited than that of d-[3,4- 14C]glucose. Likewise, the inhibitor of protein biosynthesis and the absence of Ca 2+ affected the oxidation of l-[U- 14C]leucine preferentially, relative to that of l-[1- 14C]leucine, in islets exposed to a high, but not a low, concentration of the amino acid. These results demonstrate that in pancreatic islets it is possible to dissociate both glycolysis from mitochondrial oxidative events and the oxidation of acetyl residues from their generation rate. Moreover, the experimental data suggest that nutrient-responsive and ATP-requiring functional processes exert a feedback control on mitochondrial respiration in this fuel-sensor organ.