Hew F L, Koschmann M, Christopher M, Rantzau C, Vaag A, Ward G, Beck-Nielsen H, Alford F
Department of Endocrinology and Diabetes, St. Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia.
J Clin Endocrinol Metab. 1996 Feb;81(2):555-64. doi: 10.1210/jcem.81.2.8636267.
Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.
将14名生长激素缺乏（GHD）成年人与12名年龄、性别和体重指数相匹配的对照受试者进行比较，采用基线氚标记葡萄糖平衡期和正常血糖-高胰岛素血症（约55 mU/L）钳夹技术，并结合配对肌肉活检来测量糖原合酶分数速度（FV0.1）。尽管两组总的葡萄糖处置率（Rd）基础值相似，但与对照组相比，GHD成年人胰岛素刺激后的Rd升高幅度（δ）降低了64%[分别为16.6±2.8与44.7±6.0 μmol/kg去脂体重（FFM）/分钟；P<0.001]，这主要是由于葡萄糖储存（GS）率降低（δGS，12.6±2.9与39.5±7.5 μmol/kg FFM/分钟；P<0.01）。此外，与对照值相比，GHD成年人的Rd胰岛素敏感性指数（0.39±0.07与0.85±0.11；P<0.05）和GS胰岛素敏感性指数（0.25±0.07与0.72±0.13 μmol/kg FFM/分钟每mU/L；P<0.02）均降低。GHD成年人糖酵解途径的胰岛素敏感性也降低了约50%（与对照组相比，P = 0.07）。尽管基础FV0.1相似，但GHD成年人胰岛素刺激后的FV0.1降低（0.31±0.02与0.47±0.03；P<0.005）。采用多元逐步回归分析，生长激素缺乏的持续时间、空腹甘油三酯和空腹胰岛素占Rd胰岛素敏感性指数方差的67%。总之，GHD成年人严重的胰岛素抵抗主要是由于外周组织中GS途径和糖原合酶活性受到抑制，这与生长激素缺乏的持续时间、空腹甘油三酯和空腹胰岛素有关。
