Impairment of the Pituitary-Adrenal Response to Acute Stress in Alloxan Diabetes

Abstract

The adrenal ascorbic acid depletion parameter was used to determine the pituitary-adrenal response to acute stress, the adrenal responsiveness to exogenous corticotrophin (ACTH), and the pituitary ACTH reserve in alloxan diabetes. The pituitary-adrenal response to histamine (0.5 mg/100 g i. p.) 1 hour before sacrifice was significantly impaired in uncontrolled diabetes. Elimination of glycosuria by insulin administration (7 days) restored the response to normal though adrenal hyperplasia was still evident. The impaired stress response was not due to a decrease in the adrenal responsiveness or the pituitary ACTH reserve. The adrenal ascorbic acid depletion response to exogenous ACTH (measured against saline controls) was normal. Pituitary extracts of diabetic animals produced the same degree of adrenal ascorbic acid depletion in hypophysectomized animals as pituitary extracts of normal animals. The adrenal hyperactivity previously reported to exist in uncontrolled diabetes is accompanied by a decreased ability to release preformed ACTH in response to acute stress. The metabolic stress of diabetes resembles other chronic stressors which impair the secretory mechanism at the hypothalamo-hypophyseal level.

Serum Corticosterone Levels in Rats at Various Time Intervals After Alloxanization

“…This is partly due to the somewhat different reaction of the various rat strains [Applegarth, 1949] but even more to the fact that the dura tion of the diabetic state is not always taken into consideration. When, however, a comparison between the acute and chronic diabetes was made, the chronically diabetic rats often received a lower dose of alloxan in order to assure their survival [Field, 1955;Devecerski and Frawlcij, 1963;Kraus, 1967]. Thus rats with various degrees of diabetes have been compared.…”

“…The studies of Scum and Cliernick [1960) clearly demonstrated the importance of the glucocorticoids in regard to ketosis in insulin-deficient rats. On the other hand, Kraus [1967) reported that the piluary-adrenal response to stress was impaired in alloxan diabetes. Thus the possibility cannot be ruled out that changes in the adrenocortical activity during the chronic metabolic stress of uncontrolled diabetes may be causally correlated with changes in ketosis.…”

Insulin-Induced Granuloma Tissue Formation and Angiogenesis in Alloxan-Treated Diabetic Mice

“…Insulin effect on inflammation is of particular interesting in relation to complications in diabetes. The chronic metabolic stress of uncontrolled experimental diabetes has been reported to cause adrenal hyperactivity and hyperplasia accompanied with an increase in the plasma corticosterone level (Field, 1955;Devecerski and Frawley, 1963;Kraus, 1967).…”