Crowne E C, Samra J S, Cheetham T, Watts A, Holly J M, Dunger D B
Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headington, UK.
Metabolism. 1998 Jan;47(1):31-8. doi: 10.1016/s0026-0495(98)90189-5.
To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
为研究重组人生长激素释放因子（rhIGF-I）是否能在不依赖生长激素（GH）水平的情况下对维持血糖正常所需的胰岛素剂量产生直接影响，9名胰岛素依赖型糖尿病患者（[IDDM]，7名女性；年龄、糖尿病病程及糖化血红蛋白[HbA1C]的中位数（范围）分别为16.9（12.5至21.9）岁、11.8（4.6至16.8）岁和9.8%（7.9%至14.1%））在双盲皮下注射rhIGF-I/安慰剂（40μg/kg）后进行了两项血糖正常研究（下午6:00至上午8:00）。奥曲肽输注（300ng/kg/h）抑制内源性GH，且两晚均输注三次相同的离散GH脉冲。可变速率胰岛素输注维持血糖正常。每15分钟采集一次样本（血糖和GH）、30分钟采集一次（胰岛素和中间代谢产物）、60分钟采集一次（IGF-I和非酯化脂肪酸[NEFA]）。在血糖正常的稳态期（上午4:00至8:00）分析各项变量。数据以平均值±标准误表示。注射rhIGF-I后胰岛素输注速率和游离胰岛素水平均显著降低（分别为0.13±0.03对安慰剂0.23±0.05mU/kg/min，P = 0.04，以及8.4±1.3对安慰剂12.1±1.4mU/L，P = 0.03）。rhIGF-I注射后未出现安慰剂注射后观察到的与GH脉冲相关的胰岛素需求变化。两晚的胰高血糖素水平均受到同等程度的抑制。注射rhIGF-I后胰岛素清除率未改变。两晚的NEFA和酮水平也无差异。总之，在患有糖尿病的青少年和年轻成年人中，注射rhIGF-I直接影响胰岛素需求，且与GH水平无关，但对脂肪酸或酮水平无影响。这种差异与GH脉冲后胰岛素需求变化的消除有关，提示GH和IGF-I在胰岛素作用方面存在复杂的相互作用。
