Enhanced sensitivity to insulin in rats treated with antibodies to rat growth hormone.

Abstract

Although prolonged treatment with GH can result in insulin resistance and hyperglycemia, it is not known whether endogenous GH influences sensitivity to insulin in normal animals. To investigate this possibility, sensitivity to insulin was assessed in chronically cannulated normal rats treated acutely with antiserum to rat GH (ArGH) produced in a rhesus monkey. Controls received equivalent treatment with normal monkey serum. In rats which received a regimen of six pulses of ArGH over a 24-h period, plasma glucose and insulin levels were not different from those in controls. When sensitivity to administered insulin was tested at the end of the 24-h regimen, the fall in plasma glucose was only slightly greater and more prolonged in ArGH-treated rats than in controls. However, a significant increase in sensitivity to insulin was evident in adipose tissue from the ArGH-treated rats as a greater stimulation of glucose oxidation by insulin (50 microU/ml). In addition, GH (0.5 micrograms/ml) stimulated glucose oxidation in adipose tissue from the ArGH-treated rats, while tissues from normal monkey serum-treated controls were unresponsive (refractory) to GH. The loss of the typical refractory effect of GH with ArGH treatment indicates that the biological activity of endogenous GH was neutralized. Similar results were obtained in rats treated for 6 or even 3 h with ArGH. These observations indicate that acute treatment with ArGH can neutralize GH activity and enhance sensitivity to insulin in adult rats. Thus, endogenous GH appears to participate in the regulation of carbohydrate metabolism in normal rats on an hour to hour basis.