Diabetogenic polypeptide from human pituitaries similar to that excreted by proteinuric diabetic patients

Abstract

A polypeptide exhibiting diabetogenic and antiinsulin properties has been isolated from human pituitary glands by a procedure slightly modified from that with which a similar polypeptide was previously isolated from the adenohypophysis of cattle, sheep and pigs. The isoelectric point of the compound is approximately pH 4.1 which is the same as that of the compound isolated from the adenohypophysis of the other three species and from urine of patients with lipoatrophic diabetes and proteinuric diabetics without lipoatrophy. Administration of 1 mg polypeptide per kilogram of body weight to dogs resulted in significant intolerance to glucose and resistance to exogenous insulin 10 and 34 hours after injection. Comparison of glucose tolerance tests in the same animals discloses that the diabetogenic potency of the substance from human pituitaries is much greater than that of human growth hormone or ovine prolactin. The molecular weight of the substance as determined by the dodecyl sulfate-polyacrylamide gel electrophoresis method is 20,600. A modified procedure for the isolation and purification of the polypeptide has been outlined.