AJP - Endocrinology and Metabolism, Vol 246, Issue 4 356-E360, Copyright © 1984 by American Physiological Society
Diabetogenic activity of native and biosynthetic human growth hormone in obese (ob/ob) mouse
J. L. Kostyo, S. E. Gennick and S. E. Sauder
It has been repeatedly suggested that diabetogenic activity is not an
intrinsic property of native pituitary growth hormone (GH) and that the
diabetogenic effects produced by GH preparations are due to
low-molecular-weight contaminants or degradation products of the hormone.
This possibility was evaluated in this study by assessing the ability of
purified native human GH (hGH) and biosynthetic methionyl-hGH to exacerbate
fasting hyperglycemia and glucose intolerance in the obese (ob/ob) mouse.
Native hGH that had been purified by DEAE-cellulose chromatography (A-type;
1.8 IU/mg) produced fasting hyperglycemia and glucose intolerance in the
ob/ob mouse when injected subcutaneously at doses of 50 micrograms/day or
greater for 3 days. It had no effect when a single subcutaneous dose of 200
micrograms was administered 24 h previously. To eliminate possible
contamination with smaller peptides, the hGH was gel-filtered on a column
of Sephacryl S-200 in 6 M guanidine-HCl. When injected subcutaneously into
ob/ob mice at a dose of 50 micrograms/day or greater for 3 days, the
guanidine-treated hGH produced glucose intolerance. Also biosynthetic
methionyl-hGH produced marked fasting hyperglycemia and glucose intolerance
when injected subcutaneously at doses of 50 or 100 micrograms/day for 3
days. These results support the conclusion that hGH itself is indeed
diabetogenic but that chronic exposure of the organism to the hormone is
required for its effects on glucose metabolism to become clearly manifest.
