Glutathione Potentiation of Cortisone-induced Glycosuria in the Rat.

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Abstract
Normal 300-g. rats were force-fed a high carbohydrate liquid diet and injd. intraperit. with glutathione (GSH) (5 mM/kg.) on the 18th, 32d, 45th, and 63d days of the diet. The avg. 24-hr. glucose excretion was measured by the Somogyi caramelization method. GSH injn. induced glycosuria (0.66 g./day) after the 1st injn. (18th day). Successive GSH injns. produced progressively less glycosuria and the 4th injn. (on the 63d day) produced insignificant effects (0.03 g./day). The glycosuria induced by glutathione injn. is attributed to an adaptation to the high carbo- hydrate diet rather than to the development of a tolerance to GSH. Diabetes was produced in normal rats and in subdiabetic rats by injecting cortisone in doses of 10 mg./day and 4 mg./day, respectively. Subdiabetes was produced by the prior (2-4 mos.) injn. of subthreshold doses of alloxan. When the glycosuria induced by cortisone injn. became stabilized (and after the rats were on the high carbohydrate diet for 1-2 mos.) GSH injn. (5 mM/kg.) increased the glycosuria from 2.5- to 10-fold during the 24-hr. period following the GSH injn. In some cases, glucose excretions of over 5 g./day were noted. The marked increased glycosuria occurred in cortisone diabetic rats at a time when non-diabetic controls showed insignificant responses to GSH. Cysteine and ascorbic acid also were studied. The mechanism by which GSH potentiates the diabetogenic effects of cortisone has been considered; possible factors include insulin inactivation in vivo by GSH; protection against endogenous destruction of adrenal steroids by GSH; and inactivation of an essential disulfide enzyme by GSH.