ALLOXAN ADMINISTRATION IN THE GUINEA PIG: A STUDY OF THE HISTOLOGICAL CHANGES IN THE ISLANDS OF LANGERHANS, THE BLOOD SUGAR FLUCTUATIONS, AND CHANGES IN THE GLUCOSE TOLERANCE1

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Abstract
Various dosages of alloxan were given by different routes to fasting and non-fasting guinea pigs. An effective dosage, as detd. by histological and blood sugar changes, was found to be 200 mg. alloxan per kilo body wt. admd. intraven. Pre-injn. fasting enhances the action of smaller dosages of alloxan. The maximal histological response of the guinea pig to alloxan injn. is necrosis and disappearance of nearly all of the B cells of the islands of Langerhans within the first 18-24 hrs. Recovery of the islet tissue is complete by 4 days, when heavily granulated B cells are abundant in all of the islets. The blood sugar curve after alloxan is triphasic the initial hyperglycemia reaches its peak at about 1 hr.; this is followed by a hypoglycemia becoming progressively more severe between 4 and 8 hrs.; and by 24 hrs. there is a 2d temporary hyperglycemia. The blood sugar level returns to normal by the 4th or 5th day. The glucose tolerance curve is markedly elevated for a period of several weeks after alloxan in spite of a normal fasting blood sugar level and normal-appearing islets. However, the curve is not prolonged, and in this respect more closely resembles one resulting from mild liver damage than the typical diabetic curve. Preliminary studies on the liver indicate that a decrease in hepatic parenchyma may account for the prolonged changes in carbohydrate metabolism.

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