A diabetogenic polypeptide from bovine adenohypophysis similar to that excreted in lipoatrophic diabetes

Abstract

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

The heterogeneity of bovine growth hormone. Extraction from the pituitary of components with different biological and immunological properties

“…However, the diabetogenic activity of the bovine anterior pituitary is not necessarily the exclusive property of GH-related compounds. In 1966 a polypeptide was extracted and found to be diabetogenic in man and dogs (Louis et al, 1966). This material was named bovine diabetogenic peptide and possessed neither growth-promoting activity (Tutwiler & Louis, 1971) nor lactogenic activity (Louis & Conn, 1968).…”

Pancreatic B‐cell Function and Abnormal Urinary Peptides in a Boy With Lipoatrophic Diabetes and Stenosis of the Aqueduct of Sylvius

“…Via abnormal neurohumoral signals a loss of fat in the subcutis and internal depots is induced concomitant with insulin resistance (1,21,24,29). How these signals act in detail is not known, but in both animal experiments and clinical studies, urinary peptides have been found with adipo- kinetic, diabetogenic and anti-insulin properties (7,20,21). In the diencephalic syndrome of emaciation a similar loss of subcutaneous fat occurs.…”

“…The condition is associated with hypothalamic dysfunction. It is thought that both abnormal humoral and neural stimuli may induce insulin resistance and loss of fat depots (1,6,7,20,21,22,24,26,29).…”

Insulin Action at the Molecular Level: Facts and Speculations

“…Other possibilities for active peptide fragments that come to mind are one responsible for regulation of growth and another for stimulation of lactation. The relation of the anti-insulin peptide extracted from bovine pituitaries 48 to the growth hormone fragments should be explored.…”