Studies on the Mechanism of Alloxan Initial Hyperglycemia

I. A Role of Pituitary and Adrenal Gland in Connection with the Effect of Alloxan on the Blood Sugar

Abstract

1. In hypophysectomized rats, the injection of alloxan does not cause the initial hyperglycemia and the blood sugar always falls immediately after the injection with far more marked degree than in the hypophysectomized non-alloxan-injected rats. The hypoglycemic phase is very severe and often fatal in spite of repeated administration of large amounts of glucose. But in incompletely hypophysectomized rats (1/6-1/7 of the anterior pituitary lobe remained), the typical triphasic reaction of the blood sugar as seen normal rats, is observed. So it is considered that the pituitary is playing an important role in the alloxan initial hyperglycemia.
2. The reactions obtained in adrenalectomized rats are just same with that in hypophysectomized rats. In the group of completely demedullated rats with non-regenerated cortex the curve of the blood sugar are similar to that of the adrenalectomized rats, while in the rats with regener-ated cortex it is lowered for the period of 30 minutes to 2 hours starting immediately after the alloxan injection, and then the triphasic reaction follows. Especially in cases with hypertrophically regenerated cortex the initial hyperglycemia is superimposed by permanent hyperglycemia without having secondary hypoglycemic phase. These facts reveal that the adrenal cortex is an essential factor to produce the initial hyperglycemia and the role of the adrenal medulla is to start this initial hyperglycemia immediately after the injection of alloxan.
3. The alloxan produces the significant depletion of ascorbic acid in adrenals of normal rats. So it seems that the alloxan acts as so-called stress which brings about the hyperfunction of pituitary adrenocortical system in normal rats. The author feels that this factor must not be overlooked to understand the mechanism of the alloxan initial hyperglycemia.