D-glucose Metabolism In Pancreatic Islets Research Articles

Metabolism of D-glucose anomers in pancreatic islets (Review)

D-glucose metabolism displays anomeric specificity in pancreatic islets and other cell types. Recent studies have extended this knowledge to the effect of D-glucose to augment D-fructose phosphorylation by glucokinase in both pancreatic islet B-cells and hepatocytes, and have documented that the anomeric specificity of D-glucose metabolism in pancreatic islets implies enzyme-to-enzyme tunnelling of metabolites in the early steps of glycolysis. It is proposed that the anomeric specificity of D-glucose metabolism is essential to a sound understanding of carbohydrate homeostasis in health and disease.

Effects of high extracellular K + concentrations, diazoxide and/or Ca 2+ deprivation upon d-glucose metabolism in pancreatic islets

A rise in d-glucose concentration may augment insulin release independently of changes in K + conductance or Ca 2+ influx in pancreatic islet cells, the insulinotropic action of the hexose remaining dependent on an increased generation of high-energy phosphates. In the present study, therefore, it was investigated to which extent the procedures currently used to assess the modalities of the secretory response to d-glucose independent of its effect on ATP-sensitive K + channels and Ca 2+ inflow may themselves affect the catabolism of the hexose in isolated rat pancreatic islets. A rise in the extracellular K + concentration from 5 to 30 or 60 mM failed to significantly affect the metabolism of d-glucose. At 90 mM K +, however, the maximal velocity of the glycolytic flux was decreased and the apparent K m for d-glucose lowered, without an obvious alteration of the preferential stimulation of oxidative mitochondrial events in response to a rise in d-glucose concentration. Such a preferential stimulation was abolished, however, either by diazoxide at a low, but not high, K + concentration or by Ca 2+ deprivation, in the absence or presence of diazoxide, at a high K + concentration. It is speculated that these metabolic changes may be attributable, in part at least, to an altered activity of key cytosolic (e.g. pyruvate kinase) and mitochondrial (e.g. FAD-linked glycerophosphate dehydrogenase) enzymes.

Effects of D-mannoheptulose and its hexaacetate ester upon D-glucose metabolism in rat hepatocytes.

D-mannoheptulose, which inhibits hexokinase isoenzymes in a predominantly competitive manner, has been found to decrease much more modestly D-glucose metabolism in pancreatic islets exposed to a low, as distinct from high, concentration of the hexose. In the present study, which aimed at investigating the factor(s) possibly responsible for such a phenomenon, a comparable situation was found to prevail in rat hepatocytes. However, when the hexaacetate ester of D-mannoheptulose was used instead of the unesterified heptose, the relative extent of inhibition of D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to 14C-labelled acidic metabolites was comparable in hepatocytes exposed to either 1.7 or 8.3 mM D-glucose. Moreover, at the low D-glucose level, the incorporation of 3-O-methyl-D-glucose (6.6 mM) into the incubation medium increased the inhibitory action of unesterified D-mannoheptulose upon D-glucose metabolism. These findings suggest that an insufficient uptake of the heptose accounts, in part at least, for its poor efficiency as inhibitor of D-glucose catabolism in liver, and presumably islet cells exposed to low concentrations of the hexose.