Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged

Clin Sci (Lond). 2002 Apr;102(4):457-64. doi: 10.1042/cs1020457.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Composition / drug effects
  • C-Peptide / blood
  • Calorimetry, Indirect
  • Drug Administration Schedule
  • Energy Metabolism / drug effects
  • Fatty Acids, Nonesterified / blood
  • Glucose / administration & dosage
  • Glucose Clamp Technique
  • Human Growth Hormone / pharmacology*
  • Humans
  • Insulin / blood*
  • Insulin Resistance / physiology*
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Nitrogen / metabolism
  • Oxidation-Reduction / drug effects
  • Plethysmography, Whole Body


  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Muscle Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Glucose
  • Nitrogen