Insulin-like growth factor-I in man enhances lipid mobilization and oxidation induced by a growth hormone pulse

Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27 ± 4 years, BMI 21.8 ± 1.7 kg/m²) were treated with NaCl 0.9% (saline) or IGF-I (8 μg · kg^-1 · h^-1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg^-1 · day^-1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p < 0.02) and C-peptide levels by 78% (p < 0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10 ± 0.43 (saline) to 2.79 ± 0.37 ml · 100 ml^-1 · min^-1 (IGF-I) (p < 0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9 ± 7.4 ng/ml. GH did not influence circulating levels of total IGF-I, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702 ± 267 (saline) and 885 ± 236 (IGF-I) to 963 ± 215 (saline) (p < 0.05) and 1815 ± 586 μmol/l (IGF-I) (p < 0.02), respectively; after 5 h, 3-OH-butyrate rose from 242 ± 234 (saline) and 340 ± 280 (IGF-I) to 678 ± 638 (saline) (p < 0.02) and 1115 ± 578 μmol/l (IGF-I) (p < 0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44 ± 195 to 300 ± 370 aftr 20 min (p < 0.03) and to 287 ± 91 nmol · 100 ml^-1 · min^-1 after 120 min (p < 0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.