Modulation of hepatic insulin receptors by a human growth hormone fragment (hGH 6–13)

Abstract A synthetic amino-terminal fragment of human growth hormone (hGH) containing the sequence H 2 N-Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala-COOH (hGH 6–13) was shown to increase [ 125 I]iodoinsulin binding to rat hepatic receptors in vivo. Analysis of the binding data indicated an increase in the capacity of the insulin receptors or the number of available receptors. In vitro experiments with isolated hepatocytes and hepatic plasma membranes revealed no direct interaction between the hGH 6–13 and the hepatic insulin receptors. When the isolated hepatocytes were preincubated with the synthetic hGH fragment (10 μg/ml) at 37°C for 30 min prior to tests for insulin binding, the binding of [ 125 I]iodoinsulin to the hepatic receptors was significantly enhanced. The variance between the in vivo and in vitro findings was considered in terms of the mechanism of hormonal actions mediated through a secondary cellular mediator.