Physiological Concentrations of Growth Hormone Exert Insulin-Like and Insulin Antagonistic Effects on Both Hepatic and Extrahepatic Tissues in Man*

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Abstract
To determine whether increments in circulating GH concentrations within the physiological range would exert insulin-like as well as insulin-antagonistic actions in man and, if so, whether both actions would occur in hepatic and extrahepatic tissues, normal volunteers (n = 6) were infused with human GH (hGH; 100 ng/kg-min) for 6 h along with somatostatin (100 jug/ h) to suppress insulin, glucagon, and hGH secretion and also with sufficient insulin (100 μU/kg-min) to maintain a constant plasma insulin level. During the final 2 h, glucose (2 mg/kgmin) was infused. In control studies, saline was infused instead of hGH. Infusion of hGH increased plasma hGH to 35 ng/ml. Plasma glucose decreased to 60 ± 2 mg/dl compared to 67 ± 1 mg/dl observed in control studies (P < 0.05); this greater hypoglycemia was due to both greater suppression of hepatic glucose production (P < 0.05) and greater augmentation of glucose clearance (P < 0.05). These insulin-like effects of hGH were no longer evident after 2 h. Subsequently, when glucose was infused, plasma glucose increased to 133 ± 4 mg/dl compared to the 104 ± 6 mg/dl observed in control studies (P < 0.01). This greater hyperglycemia was due to both impaired suppression of hepatic glucose production (P < 0.001) and decreased glucose clearance (P < 0.01). These results indicate that physiological increments in plasma hGH cause both insulin-like and insulin-antagonistic effects in man and that these actions occur in hepatic as well as extrahepatic tissues. The insulin-like actions of hGH are transient.