title: Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged.
abstract: The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05 mg.24 h(-1).kg(-1)) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[(2)H(5)]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P<0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P<0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P<0.05). In addition, 24 h urinary nitrogen excretion decreased by 26% (P<0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P<0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.
authors.affiliation: Centre for Gastrointestinal Disease, Ersta Hospital, Box 4622, Karolinska Institute, 116 91 Stockholm, Sweden. jonas.nygren@ersta.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Nygren
authors.forename: Anders
authors.initials: A
authors.lastname: Thorell
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.forename: Pia
authors.initials: P
authors.lastname: Essén
authors.forename: Jan
authors.initials: J
authors.lastname: Wernerman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McNurlan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Garlick
authors.forename: Olle
authors.initials: O
authors.lastname: Ljungqvist
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002153:Calorimetry, Indirect; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010993:Plethysmography, Whole Body
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D009124:Muscle Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D009584:Nitrogen