EFFECT OF ELEVATED GLUCOSE CONCENTRATIONS ON THE OXIDANT SENSITIVITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENT ERYTHROCYTES

Abstract

Diabetic acidosis is known to trigger hemolysis in patients with G6PD deficiency. Elevated glucose concentrations activate hexonate dehydrogenase, oxidize NADPH, and hence stimulate the hexose monophosphate (HMP) shunt. The present studies investigated whether HMP shunt activation, in the presence of increased glucose concentrations, significantly increased the vulnerability of G6PD deficient RBC's to oxidant injury. In normal RBC's, both the resting and ascorbate-stimulated HMP shunt (glucose-1-14C oxidation to 14CO2) were greater in 50 than 5 mM glucose. Glutathione regeneration in diamide-treated normal RBC's was the same at 5 and 50 mM glucose. Hydroxylaminedapsone, which requires NADPH for drug activation and maximal hemoglobin oxidation, produced more methemoglobin in normal than G6PD deficient cells, but no difference was seen when the effects of 5 and 50 mM glucose were compared. Sulfhemoglobin formation in G6PD deficient RBC's incubated with cyanide and ascorbate was not significantly different in 5 or 50 mM glucose. These data indicate that NADPH-dependent reactions vital for hemoglobin protection are not affected adversely by increased glucose concentrations. Thus, it is unlikely that hyperglycemia significantly alters the reductive potential of G6PD deficient RBC's during an oxidant stress such as infection.