Mechanism of the Diabetogenic Action of Alloxan.∗

Alloxan has been found to produce sustained diabetes mellitus in rats, rabbits, and dogs (Shaw-Dunn and McLetchie, 1 Goldner and Gomori, 2 , 3 Bailey and. Bailey 4 ). This diabetes is due to degeneration of the beta cells in the islets of Langerhans (Shaw-Dunn, Sheehan and McLetchie 5 ) and consequently to the decrease of insulin production (Goldner and Gomori 6 ). Prior to the establishment of the diabetic syndrome the blood sugar of the rabbit shows a characteristic biphasic reaction, which was fist described by Jacobs. 7 Animmediate hyperglycemia which reaches its peak within 2 or 3 hours in followed by a severe. Often fatalhypoglycemia, which after a duration of 15 to 20 hours yields to the ultimate hyperglycemia and glycosuria. The hypoglycemic phase is explained by Show Dunn and co-workers 5 as the effect of large amounts of insulin, which are released suddenly from the degenerating beta cells. The phenomenon of the initial hyperglycemia raises the question whether alloxan inhibits insulin before it destroys the site of insulin production. It seemed, therefore, of interest to investigate the question whether insulin is able to prevent the initial rise of the blood sugar after alloxan poisoning and also whether insulin can protect the beta cells against alloxan injury. The latter problem seemed of special interest, since it has been found that insulin treatment and the maintenance of a normal blood sugar level will protect animals against the diabetogenic effect of anterior pituitary extract (Campbell, Haist, Ham, and Best8). Experimental Procedure. Three rabbits out of a series of 6 of the same size and breed were treated simultaneously with a diabetogenic dose of alloxan and with insulin, the 2 substances being injected into 2 different veins, the remaining 3 animals with the same doses of a mixture of alloxan and insulin, kept at room temperature for 60 minutes prior to intravenous injection.