Glutathione depletion: a risk factor for impaired glucose regulation

A deficiency of the antioxidant glutathione (GSH) in various pathophysiologic conditions, is associated with impaired blood glucose regulation (IGR). AIM: To examine the possibility that GSH depletion is a cause of IGR. METHODS : Male Sprague-Dawley rats (200-290g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a cage that allowed free movement, with access to water and chow. Two hours after waking, the rats were infused at the rate of lml/hr with either normal saline (control,n=l4), saline+10 mM L-buthionine-S_R-sulfoximine IBSO-an inhibitor of GSH synthesis, n=8) , or saline+BSO+10 mM GSH monoethyl ester (n=i8). After 48 hours, the rats were sacrificed and blood samples again obtained for assay of plasma glucose and insulin, and whole blood GSH. RKggLTg: Data were expressed as mean ±SEM. No differences in food intake and body weights were observed among groups after infusion. In the control and BSO+GSH groups, plasma glucose levels remained normal after nfusion. However,in the saline+BSO group, plasma glucose ncreased significantly from 116 ±5.65 to 161 ±7.75 mg/dl (p 0.01) . Plasma insulin levels rose only slightly in the group nfused saline alone and not in the BSO+GSH group, while in he saline+BSO group, plasma insulin levels rose significantly from 278.5 ±52.57 to 723.88 ±53.33 pg/ml (p < 0.01). A modest reduction in blood GSH was seen following saline infusion but a profound decrease after saline+BSO (72S+.33 vs 105±55 μmol/L, p<0.001), which was not replenished by the addition of 10 mM GSH ester to the infusate. CONCLUSION: GSHdepleted rats develop IGR which is corrected by exogenous GSH supplementation.

Duke Scholars

Author John Palmer Grant Surgery, Minimally Invasive Surgery