Diabetogenic peptide from human growth hormone: partial purification from peptic digest and long-term action in ob/ob mice.
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 have been 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 G25; these active fractions exhibited multiple NH2-terminal (Lys, Phe, Leu, and Tyr). Fraction CD has these characteristics: (i) It induces glucose intolerance in fasting female ob/ob mice when injected subcutaneously 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 months after a single glucose tolerance test. (ii) It is a peptide smaller than that reported to stimulate body growth, but larger than somatostatin. This peptide, as reported earlier, does not crossreact with antiserum to human growth hormone in radioimmunoassay.
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced*; D005260:Female; D013006:Growth Hormone / Q000032:analysis; D051379:Mice; D008820:Mice, Obese; D008970:Molecular Weight; D010455:Peptides / Q000302:isolation & purification*; D013329:Structure-Activity Relationship; D013997:Time Factors
D001786:Blood Glucose; D010455:Peptides; D013006:Growth Hormone