STUDIES ON PRODUCTION AND PREVENTION OF ALLOXAN DIABETES

Abstract

From the following experimental results, it was suggested strongly that two systems other than the pancreas, the pituitaryadrenal system and autonomic nervous system, are also important in the pathogenesis of production and prevention of alloxan diabetes.1) 40mg/kg of alloxan was intravenously injected into rats of Wistar strain, and the development of alloxan diabetes was observed in 77%, 62 out of 80 rats.2) The pancreas in the rats that developed alloxan diabetes showed morphological changes such as reduction of the islets of Langerhans and destruction of β-cells. Biochemically, a decrease of glutathion content in the pancreas was observed.3) Alloxan diabetic rats showed a marked decrease of ascorbic acid content in the adrenal gland and a decrease in the number of circulating eosinophils, suggesting hyperfunction of the adrenal gland. Dysfunction of the autonomic nervous system was inplicated from a decrease of cholinesterase activity in plasma.4) In rats treated by 5mg/kg of intramuscular injection of chlorpromazine given 30 minutes prior to intravenous injection of 40mg/kg of alloxan, the development of alloxan diabetes was suppressed to 31%, 36 out of 117 rats, at 14°-16°C.5) In the cases in which the development of alloxan diabetes was prevented by chlorpromazine, the pathological changes in the pancreas was less marked and glutathion content in the pancreas were nearly normal.6) The premedicatian of chlorpromazine suppressed the decrease of ascorbic acid content in the adrenal gland and the decrease in the number of circulating eosinophils of alloxan treated rats. At the same time chlorpromazine showed inhibitory effect on the decline of plasma cholinesterase activity.7) Simultaneous intramuscular injection of 5 units of ACTH together with 5mg/kg of chlorpromazine could not prevent the development of diabetes caused by intravenous injection of 40mg/kg of alloxan given 30 minutes thereafter.