Reversal of diet-induced catabolism by infusion of recombinant insulin-like growth factor-I in humans.
Treatment of catabolic conditions with insulin-like growth factor I (IGF-I), the peptide that mediates some of the anabolic growth-promoting effects of GH, offers potential advantages of avoiding the hyperglycemia caused by treatment with GH. A state of moderate catabolism was produced in six normal, young adult volunteers by restricting their daily dietary intake to 20 kilocalories/kg/day. During the last 6 days of two 2-week diet-study periods, they received either IGF-I (12 micrograms/kg/h by i.v. infusion over 16 h) or GH (0.05 mg/kg/day by sc injection). IGF-I improved nitrogen balance from -236 +/- 45 mmol/day (+/- SE) during diet alone, to -65 +/- 40 mmol/day (P less than 0.001) during the last 4 days of IGF-I infusion. A similar effect was produced by GH. IGF-I infusion decreased fasting blood glucose from 4.94 +/- 0.91 mmol/L to 3.13 +/- 0.44 mmol/L (P less than 0.001), while GH raised blood glucose values (4.75 +/- 1.01 mmol/L on diet alone, to 5.48 +/- 1.00 during the period of GH treatment; P less than 0.05). Despite these differences in blood glucose, IGF-I infusions decreased serum insulin (74.9 +/- 26.8 pmol/L on diet alone, to 16.7 +/- 1.5 pmol/L during IGF-I) and serum connecting-peptide concentrations (2.14 +/- 0.89 mmol/L on diet alone, to 0.97 +/- 0.14 during IGF-I), while GH raised insulin (109.4 +/- 31.3 pmol/L, P less than 0.05 during GH) and connecting-peptide (3.12 +/- 0.59 mmol/L, P less than 0.02). At the dose of each hormone used, the attenuation of nitrogen wasting produced by infusions of IGF-I was similar in magnitude and timing to that produced by injections of GH. The reduction in serum glucose concentrations produced by IGF-I compared with the increase in glucose noted during GH treatment, could benefit hyperglycemic catabolic patients.
Clemmons
D R
DR
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599.
Smith-Banks
A
A
Underwood
L E
LE
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D050260:Carbohydrate Metabolism; D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects*; D005215:Fasting; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009584:Nitrogen / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015430:Weight Gain
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D009584:Nitrogen