Amino-terminal peptide of growth hormone enhances insulin action in normal rats.
Earlier studies demonstrated that the 20K-dalton variant of human GH (hGH), which differs from hGH by deletion of the amino acid residues 32-46, has decreased insulin-like activity. The current study assessed whether a peptide representing this deleted region could enhance insulin-stimulated glucose uptake in the intact rat and if this effect was localized in liver and/or muscle. Peptides hGH-(32-46) and rat GH-(32-45) were used in these studies. Assessment of the action of a peptide was done by determining its effect on the steady state serum glucose (SSSG) concentration during an insulin suppression test. Glucose was infused alone and with two rates of infusion of insulin. The data indicated that neither of the GH peptides affected SSSG in the absence of exogenously administered insulin or at low (40 microU/ml) serum levels of insulin, but when serum insulin was increased to 77 microU/ml, a significant (P less than 0.05) decrease in SSSG was produced by the peptides. In subsequent studies isolated liver and hind limb skeletal muscle were perfused with a solution of hGH-(32-46). Basal glucose release from the liver was suppressed by both hGH-(32-46) and insulin alone, and this decrease was not enhanced by combining insulin with hGH-(32-46). Glucose uptake by skeletal muscle, expressed as a metabolic clearance constant (k), was enhanced by infusion of insulin and further increased with added peptide. Basal uptake was 6.67 microliter/min.g muscle; uptake was 8.17 microliter/min.g (P less than 0.01) after addition of 128 microU/ml insulin. This increased still farther to 9.24 microliter/min.g (P less than 0.05) when peptide was administered with insulin. These findings suggest that GH peptides independently suppress glucose outflow from the liver and potentiate insulin action by facilitating glucose uptake by peripheral tissues.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C051660:somatotropin (32-46); D013006:Growth Hormone; D006006:Glycogen Synthase; D005947:Glucose