EFFECT OF CHRONIC GROWTH-HORMONE TREATMENT ON INSULIN SIGNAL-TRANSDUCTION IN RAT-TISSUES

Growth hormone (GH) is known to produce insulin resistance, but the ex act molecular mechanism remains unclear. We have chronically treated r ats with GH and observed that the levels of insulin receptor in the li ver or muscle were similar in both the GH-treated and non-treated rats . Insulin-stimulated receptor autophosphorylation was unaltered in the liver, but was reduced in the muscle of rats treated with GH. Insulin receptor substrate-1 (IRS-1) and phosphatidylinositol (PI) 3-kinase p rotein levels decreased in the liver but not muscle of GH-treated rats . There was no change in hepatic and muscle IRS-2 concentrations. A co mmon finding in liver and muscle was the decrease in IRS-1 and IRS-2 t yrosine phosphorylation associated with a reduction in the interaction between these substrates and PI 3-kinase. These data suggest that cha nges in the early steps of insulin signal transduction may have a role in the insulin resistance observed in rats exposed to an excess of GH . (C) 1997 Elsevier Science Ireland Ltd.