Physiological Concentrations of Growth Hormone Exert Insulin-Like and Insulin Antagonistic Effects on Both Hepatic and Extrahepatic Tissues in Man*
LINDA R. MACGORMAN,
ROBERT A. RIZZA and
JOHN E. GERICH
Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota 55905
Address requests for reprints to: Dr. John E. Gerich, Departments of Medicine and Physiology, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55901.
To determine whether increments in circulating GH concentrationswithin the physiological range would exert insulin-like as wellas insulin-antagonistic actions in man and, if so, whether bothactions would occur in hepatic and extrahepatic tissues, normalvolunteers (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 insulinlevel. 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 glucosedecreased to 60 ± 2 mg/dl compared to 67 ± 1 mg/dlobserved in control studies (P < 0.05); this greater hypoglycemiawas 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 longerevident after 2 h. Subsequently, when glucose was infused, plasmaglucose 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 suppressionof hepatic glucose production (P < 0.001) and decreased glucoseclearance (P < 0.01).
These results indicate that physiological increments in plasmahGH cause both insulin-like and insulin-antagonistic effectsin man and that these actions occur in hepatic as well as extrahepatictissues. The insulin-like actions of hGH are transient.
* This work was supported by grants from the NIAMDD (Am-20411,RR-00036, and AM-00648), the Mayo Foundation, and the NationalFoundation-March of Dimes.
Received November 24, 1981.
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