人体内的胰岛素样生长因子-I可增强生长激素脉冲诱导的脂质动员和氧化。

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

作者信息

Bianda T L, Hussain M A, Keller A, Glatz Y, Schmitz O, Christiansen J S, Alberti K G, Froesch E R

机构信息

Department of Internal Medicine, University Hospital, Zürich, Switzerland.

出版信息

Diabetologia. 1996 Aug;39(8):961-9. doi: 10.1007/BF00403916.

DOI:10.1007/BF00403916

PMID:8858219

Abstract

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 micrograms.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.100ml-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 mumol/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 mumol/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 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 ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.

摘要

在给予胰岛素样生长因子-I（IGF-I）期间，生长激素（GH）的分泌受到抑制。本研究的目的是检验IGF-I是否会改变对GH脉冲的代谢反应。7名健康男性受试者（年龄27±4岁，体重指数21.8±1.7kg/m²）以随机交叉方式，通过皮下持续输注0.9%氯化钠溶液（生理盐水）或IGF-I（8微克·千克⁻¹·小时⁻¹），持续5天，同时接受等热量饮食（30千卡·千克⁻¹·天⁻¹）。在治疗的第三天，静脉推注0.5U GH。通过测量动脉化和深静脉血样来检测前臂肌肉代谢，通过阻断体积描记法检测前臂血流量，通过间接量热法检测底物氧化。通过曲线下面积评估，IGF-I治疗使胰岛素浓度显著降低80%（p<0.02），C肽水平降低78%（p<0.02）。非酯化脂肪酸（NEFA）、甘油和3-羟基丁酸水平升高，丙氨酸浓度降低。前臂血流量从2.10±0.43（生理盐水）升至2.79±0.37毫升·100毫升⁻¹·分钟⁻¹（IGF-I）（p<0.02）。GH脉冲：静脉注射GH后10小时，血清GH峰值达到40.9±7.4纳克/毫升。GH不影响总IGF-I、C肽、胰岛素或葡萄糖的循环水平，但导致NEFA、甘油和3-羟基丁酸水平进一步升高，表明脂肪分解和生酮作用增强。在IGF-I治疗期间，GH的这种作用更为明显：NEFA分别从702±267（生理盐水）和885±236（IGF-I）升至963±215（生理盐水）（p<0.05）和1815±586微摩尔/升（IGF-I）（p<0.02）；5小时后，3-羟基丁酸分别从242±234（生理盐水）和340±280（IGF-I）升至678±638（生理盐水）（p<0.02）和1115±578微摩尔/升（IGF-I）（p<0.02）。注射GH后，仅在接受IGF-I治疗的受试者中，前臂对3-羟基丁酸的摄取显著升高：20分钟后从44±195升至300±370（p<0.03），120分钟后升至287±91纳摩尔·100毫升⁻¹·分钟⁻¹（p<0.02）。总之，在IGF-I治疗期间，对GH的脂肪分解和生酮反应明显增强，骨骼肌对酮体的利用增加。