Effect of Irradiation of Hypophysis on Experimental Diabetes

Abstract

Various investigators have presented evidence to show that the hypophysis plays an important rôle in carbohydrate metabolism. The first conclusive evidence is that of Houssay and coworkers, who found (1) that extracts of the anterior lobe of the hypophysis injected into normal dogs produce hyperglycemia, glycosuria and ketonuria, and when injected into depancreatized dogs, an increase in severity of the diabetes; 1 , 2 (2) that removal of the hypophysis in normal dogs leads to a hypersensitivity to insulin, 3 hypoglycemic convulsions during fasting, and an increased tolerance to glucose; 4 , 5 (3) that in depancreatized dogs, removal of the hypophysis restores the carbohydrate metabolism to an approximately normal condition, but renders the animal hypersensitive to insulin; 6 , 7 that injection of active anterior-lobe extracts causes a reappearance of the symptoms of diabetes in hypophysectomized-depancreatized dogs. 8 These findings have been largely confirmed by the work of Evans et al., 9 Barnes and Regan, 10 Daggs and Eaton, 11 and Corkill et al. 12

Since the removal of the hypophysis decreases the symptoms of experimental diabetes, it was thought that destructive doses of X-ray to the hypophysis might produce similar results.

Six dogs were depancreatized and allowed to recover under insulin administration. About one week after operation they were placed on a basic diet of dog biscuits, cane sugar and freshly ground meat, to which was added liberal amounts of fresh or dried pancreas. Approximately 2 units of insulin per kilo body weight were given twice daily at the time of feeding. After the wound had healed completely, usually within 3 weeks, food and insulin were withheld for a period of 18 to 20 hours, and the tolerance of the animal to orally administered glucose was determined. After taking an initial blood sample, 1.75 gm. glucose per kilo was given by stomach tube, and further blood samples were taken at 15, 45, 75, and 105 minute intervals. Blood sugar was determined by Folin's method.