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. Toe aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healt hy male subjects (age 27 +/- 4 years, BMI 21.8 +/- 1.7 kg/m(2)) were t reated with NaCl 0.9% (saline) or IGF-I (8 mu g . kg(-1). h(-1)) for 5 days by continuous subcutaneous infusion in a randomized, crossover f ashion 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 admin istered. Forearm muscle metabolism was examined by measuring arteriali zed and deep venous blood samples, forearm blood flow by occlusion ple thysmography and substrate oxidation by indirect calorimetry. IGF-I tr eatment 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 l evels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10 +/- 0.43 (saline) to 2.79 +/- 0.37 ml . 100ml(-1) . min(-1) (IGF-I) (p < 0.02). GH-pulse: 10 h after i.v. GH injection s erum GH peaked at 40.9+/-7.4 ng/ml. GH did not influence circulating l evels of total IGF-I, C-peptide, insulin or glucose, but caused a furt her increase in NEFA, glycerol and 3-OH-butyrate levels, indicating en hanced lipolysis and ketogenesis. This effect of GH was much more pron ounced during IGF-I: NEFA rose from 702 +/- 267 (saline) and 885 +/- 2 36 (IGF-I) to 963 +/- 215 (saline) (p < 0.05) and 1815 +/- 586 mu mol/ 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 mu mol/l (IGF-I) (p < 0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly el evated only in the subjects treated with IGF-I: from 44 +/- 195 to 300 +/- 370 after 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 ket ogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.