Effects of growth hormone and IGF-I on glucocorticoid-induced protein catabolism in humans.
The effects of similar increases in total insulin-like growth factor I (IGF-I) plasma concentrations achieved by either recombinant human (rh) growth hormone (GH) or rhIGF-I administration on whole body protein and glucose kinetics were assessed. Twenty-six healthy subjects received methylprednisolone (0.5 mg.kg-1.day-1 orally) during 6 days in combination with either placebo (saline sc), GH (0.3 mg.kg-1.day-1 sc), or IGF-I (80 micrograms.kg-1.day-1 sc) in a double-blind randomized fashion. Glucocorticoid administration resulted in protein catabolism as indicated by an increase in leucine flux and a 62 +/- 13% increase in leucine oxidation ([1-13C]leucine infusion technique); this increase was abolished by GH (-1 +/- 18%) as was statistically insignificant during IGF-I treatment (+53 +/- 25%). GH increased endogenous glucose production by 28 +/- 8%, augmented glucocorticoid-induced insulin resistance of peripheral glucose clearance (euglycemic clamp), and increased circulating lipids. IGF-I administration resulted in both increased endogenous glucose production and increased peripheral glucose clearance such that plasma glucose concentrations remained unchanged by IGF-I. IGF-I lowered circulating GH and insulin and altered IGF binding proteins, which all may have reduced bioactivity of IGF-I. The data demonstrate that, in spite of similar total IGF-I plasma concentrations during treatment, GH and IGF-I exert markedly different effects on whole body leucine, glucose, and lipid metabolism.
Oehri
M
M
Department of Research and of Internal Medicine, University Hospital Basel, Switzerland.
Ninnis
R
R
Girard
J
J
Frey
F J
FJ
Keller
U
U
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008775:Methylprednisolone / Q000097:blood / Q000494:pharmacology*; D010187:Pancreatic Hormones / Q000097:blood; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins
D001786:Blood Glucose; D002096:C-Peptide; D018969:Insulin-Like Growth Factor Binding Proteins; D010187:Pancreatic Hormones; D011506:Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D007930:Leucine; D008775:Methylprednisolone