Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged.
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.
Nygren
Jonas
J
Centre for Gastrointestinal Disease, Ersta Hospital, Box 4622, Karolinska Institute, 116 91 Stockholm, Sweden. jonas.nygren@ersta.se
Thorell
Anders
A
Brismar
Kerstin
K
Essén
Pia
P
Wernerman
Jan
J
McNurlan
Margaret A
MA
Garlick
Peter J
PJ
Ljungqvist
Olle
O
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
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