Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle
Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle
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DOI：
10.1210/jc.2002-020542
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发表时间：
2003-04-01
影响因子：
5.8
通讯作者：
Groop, L
中科院分区：
文献类型：
--
作者：
Bramnert, M;Segerlantz, M;Groop, L
生长激素替代疗法对能量代谢的影响仍然不确定，增加肌肉质量的长期益处被认为超过短期的负面代谢影响。本研究旨在通过检查短期（1周）和长期（6个月）低剂量的影响（9.6 μ g/kg体重。d）GH替代疗法或安慰剂对全身葡萄糖和脂质代谢的影响（口服葡萄糖耐量试验和正常血糖高胰岛素钳夹结合间接量热法和输注3-[H-3]葡萄糖）和肌肉组成和肌肉酶/GH治疗导致胰岛素刺激的葡萄糖摄取在1周（-52%; P = 0.008）和6个月（-39%; P = 0.008）时受损，这与葡萄糖耐量恶化相关（r = -0.481; P = 0.003）。葡萄糖摄取减少与1周（60%; P = 0.008）和6个月（60%; P = 0.008）时脂质氧化增加以及葡萄糖氧化减少相关。GH治疗期间糖代谢的恶化也与脂质氧化速率的增加相关（r = -0.508; P = 0.0002）。此外，有一个转向更多的糖酵解II型纤维在GH therapeutic.In结论，替代疗法与低剂量GH缺乏的成人受试者与持续恶化的葡萄糖代谢作为一个后果的GH的脂解作用，导致脂质底物的氧化增强。此外，在肌肉中观察到向更多胰岛素抵抗II X型纤维的转变。在长期GH替代治疗期间，应仔细监测葡萄糖代谢。
The effects of GH replacement therapy on energy metabolism are still uncertain, and long-term benefits of increased muscle mass are thought to outweigh short-term negative metabolic effects. This study was designed to address this issue by examining both short-term (1 wk) and long-term (6 months) effects of a low-dose (9.6 mug/kg body weight.d) GH replacement therapy or placebo on whole-body glucose and lipid metabolism (oral glucose tolerance test and euglycemic hyperinsulinemic clamp combined with indirect calorimetry and infusion of 3-[H-3]glucose) and on muscle composition and muscle enzymes/metabolites, as determined from biopsies obtained at the end of the clamp in 19 GH-deficient adult subjects.GH therapy resulted in impaired insulin-stimulated glucose uptake at 1 wk (-52%; P = 0.008) and 6 months (-39%; P = 0.008), which correlated with deterioration of glucose tolerance (r = -0.481; P = 0.003). The decrease in glucose uptake was associated with an increase in lipid oxidation at 1 wk (60%; P = 0.008) and 6 months (60%; P = 0.008) and a concomitant decrease in glucose oxidation. The deterioration of glucose metabolism during GH therapy also correlated with the enhanced rate of lipid oxidation (r = -0.508; P = 0.0002). In addition, there was a shift toward more glycolytic type II fibers during GH therapy.In conclusion, replacement therapy with a low-dose GH in GH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of GH, resulting in enhanced oxidation of lipid substrates. Also, a shift toward more insulin-resistant type II X fibers is seen in muscle. Glucose metabolism should be carefully monitored during long-term GH replacement therapy.