Nonmammalian Growth Hormones Have Diabetogenic and Insulin-Like Activities*

Purified GHs isolated from ostrich, sea turtle, snapping turtle, bullfrog, Tilapia, and sturgeon were tested for in vivo diabetogenic activity in the hereditarily obese ob/ob mouse and for in vitro insulin-like activity in isolated adipose tissue from hypophysectomized rats. GHs from all species exhibited significant diabetogenic activity, causing fasting hyperglycemia and decreased glucose tolerance when administered at doses of 100 micrograms/day (ostrich, bullfrog, and sturgeon) or 200 micrograms/day (sea turtle, snapping turtle, and Tilapia) for 3 days. Similar responses were obtained when purified human GH was administered at a dose of 10 micrograms/day for 3 days. GHs from most species also exhibited significant insulin-like activity, stimulating increased [14 C]glucose oxidation to 14CO2 by isolated adipose tissue from hypophysectomized rats when employed at concentrations of 50 nM (bullfrog), 250 nM (sturgeon), 500 nM (ostrich), or 2500 nM (sea turtle and Tilapia). Purified human GH gave similar responses at concentrations of 2.5-5 nM in this assay. These results support the hypothesis that diabetogenic and insulin-like activities are intrinsic properties of GH and provide strong evidence that the structural determinants for diabetogenic and insulin-like activities arose early in the evolution of the GH molecule.