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At the level of the pituitary, in vitro studies of pituitary cells and in vivo findings in mice harvesting a somatotroph-specific knockout of the insulin receptor have demonstrated that insulin directly suppressed pituitary GH secretion independent of the IGF-I receptor (IGF-IR) ( in vitro studies using the human hepatoma cell line (HuH7) as a model have shown that insulin stimulates GHR protein synthesis and GHR binding of GH in a dose-dependent manner ( in vivo studies based on rodents have shown reduced hepatic GHR expression ( Furthermore, besides regulating circulating IGF-I levels via its impact on the hepatic GH sensitivity, insulin also inhibits hepatic synthesis and secretion of IGF-binding protein-1 (IGFBP-1)

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These enzymatic activities underpin many of the compounds observed effects on connective tissue and cellular defense mechanisms