A polypeptide has been isolated from bovine adenohypopbysis which antagonizes the hypoglycemic effect of exogenous insulin and which, per se, induces loss of carbohydrate tolerance in men and dogs. Mild acid hydrolysis of the active polypeptide yields a compound which retains the same biological properties. Characteristics of the active principle and its hydrolytic product is the long duration of their activities, the greatest intensity of the effects TN RECENT COMMUNICATIONS being observed between 34 and 60 hours after a single intramuscular injection. Both substances are devoid of ACTH activity. The active polypeptide resembles closely the insulin antagonist isolated from the urine of patients with lipoatrophic diabetes previously reported from this laboratory. Details of the isolation and physiologic effects of the active substance and its hydrolytic product are described. (Metabolism 15: No. 4, April, 308-324, 1966) from this laboratory,1*2 the isolation1 of an insulin antagonist from the urine of patients with lipoatrophic diabetes has been reported. It also was demonstrated that a similar substance was present in the urine of a maturity-onset insulin-resistant diabetic without lipoatrophy. The substance was found to be a polypeptide which when administered to either dogs or man exhibited diabetogenic and anti-insulin effects. The origin of the active principle had not been determined. The present report describes a procedure for the isolation of a similar substance from the anterior lobes of bovine pituitary glands. Like the insulin antagonist from the urine, the material is also highly active both in dogs and in man.
MATERIALS AND METHODSFrozen bovine anterior pituitary glands, obtained from the Armour Pharmaceutical Company, Kankakee, Illinois, were treated according to the procedure shown in Figure 1. The
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