Influence of Age on Responsiveness to Diabetogenic Action of Growth Hormone

Responsiveness to the growth-promoting action of growth hormone (GH) develops gradually during postnatal life, and as the organism ages, sensitivity to the hormone declines. Our study was undertaken to determine whether there is a similar age-related pattern of sensitivity to the diabetogenic action of purified native human GH (hGH) in the obese (ob/ob) mouse. The ob/ob mouse was used because adults of this strain respond to chronic GH treatment with increases in fasting plasma insulin and blood glucose concentrations and with glucose intolerance. When hGH was given subcutaneously to adult (4-mo-old) female mice at doses of 5, 10, or 25 μg/day for 3 days, a significant increase in fasting blood glucose concentration and animpairment in glucose tolerance were produced by the 10-μg/day dose. Larger effects were obtained with the 25-μg/day dose. A threefold increase in fasting plasma insulin concentration was also produced with this dose of the hormone. By contrast, 25 μg/day of hGH had no effect on fasting plasma insulin, blood glucose, or glucose tolerance in 1-mo-old ob/ob mice. When a dose of 100 μg/day of hGH was given to 1-mo-old animals, a significant increase in fasting plasma insulin concentration occurred, but again there were no effects on fasting blood glucose or glucose tolerance. Mice 1.5 mo old showed marginal changes in fasting blood glucose and glucose tolerance when given hGH at doses of 25 or 100 μg/day. Mice 9 or 12 mo old exhibited responsiveness similar to that of 4-mo-old animals. Thus, responsiveness to the diabetogenic action of GH develops gradually in the ob/ob mouse during postnatal growth. However, there does not appear to be a significant decline in sensitivity to the diabetogenic action of GH as the adult animal ages.