Thymus involution and inhibition of spleen growth accompanies streptozotocin-induced diabetes in rats; possible relationship of these changes to the elevated hydrolase levels in diabetic plasma

Diabetes in man and rats is accompanied by increased levels of acid hydrolases in plasma and urine, the increase being reversed by insulin. In investigating possible tissue sources of the additional enzymes, the unexpected observation was made that streptozotocin-induced diabetes in rats is accompanied by substantial involution of the thymus and the failure of the spleen to grow at its normal rate. One week after streptozotocin treatment, the average thymus weight of diabetic rats was 30% less than that of age-matched control rats. Eight weeks after the induction of diabetes, only 10 to 20% of the thymus remained. At that time, the spleen weight was only 50% that of age-matched controls. The organ weight changes were paralleled by changes in the organ levels of acid hydrolases. The changes were all reversed by insulin treatment. Since it appeared possible that corticosteroids might be the mediators of the streptozotocin-induced changes, the effects of streptozotocin were determined in adrenalectomized rats. The decreases in thymic and splenic weights again were observed, as well as decreases in most organ hydrolases and increases in most plasma hydrolases. Clearly, the principal streptozotocin effects are not adrenal dependent. Although analyses of hexosaminidase A and B levels in various tissues and plasma suggested that the thymus and spleen may contribute to the additional hydrolases found in diabetic plasma, other factors must also be involved.