Diabetogenic peptide from human growth hormone: partial purification from peptic digest and long-term action in ob/ob mice.

Abstract

Studies in female ob/ob mice demonstrated diabetogenic properties of human growth hormone (somatotropin) and of a fragment generated therefrom by controlled digestion with pepsin; both the fragment and parent growth hormone produce long-term effects on carbohydrate metabolism; in acute glucose tolerance tests, only the fragment is active. Two nonacidic diabetogenic fractions were separated from inactive fractions by chromatography on Bio-Gel P-6 followed by ion exchange chromatography at pH 4.3 and gel filtration on Bio-Gel P-2 and/or Sephadex G-25; these active fractions exhibited multiple NH2-termini (Lys, Phe, Leu and Tyr). Fraction CD i.e. induces glucose intolerance in fasting female ob/ob mice when injected s.c. in a divided dose, 15 min before and concurrently with glucose; mice injected with sufficient peptide exhibit elevated fasting glucose levels as long as 7 mo. after a single glucose tolerance test. It is a peptide smaller than that reported to stimulate body growth but larger than somatostatin. This peptide does not crossreact with antiserum to human growth hormone in radioimmunoassay.