Lee Ada P, Mulligan Kathleen, Schambelan Morris, Murphy Elizabeth J, Weiss Ethan J
Department of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA.
Division of Endocrinology, San Francisco General Hospital, San Francisco, CA, 94110, USA.
F1000Res. 2017 May 3;6:614. doi: 10.12688/f1000research.11359.1. eCollection 2017.
Growth hormone (GH) is known to affect insulin and glucose metabolism. Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men. Four men between the ages of 18-62 with a BMI of 18-35kg/m , with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily. Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques. Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3 3.4 ± 2.4; = 0.82), as well as suppression of EGP (89.7 ± 26.9 83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1% 61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment. Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.
已知生长激素（GH）会影响胰岛素和葡萄糖代谢。在肢端肥大症患者中阻断其作用可改善糖尿病和葡萄糖代谢。我们旨在确定聚乙二醇化重组人生长激素受体拮抗剂培维索孟对胰岛素抵抗的非糖尿病男性的胰岛素抵抗、内源性葡萄糖生成（EGP）和脂肪分解的影响。4名年龄在18 - 62岁、体重指数为18 - 35kg/m²、胰岛素抵抗定义为稳态模型评估的胰岛素抵抗指数（HOMA-IR）> 2.77的男性，每天接受20mg培维索孟治疗4周。治疗前后进行住院代谢评估。主要观察指标为：培维索孟治疗后通过高胰岛素正常血糖钳夹测定的胰岛素敏感性变化；以及通过稳定同位素示踪技术评估的EGP和脂肪分解。治疗4周后，胰岛素样生长因子-1（IGF-1）浓度从134.0±41.5（平均值±标准差）降至72.0±11.7 ng/mL（p = 0.04）。培维索孟治疗期间，全身胰岛素敏感性指数（M/I 3.2±1.3对3.4±2.4；p = 0.82），以及EGP抑制率（89.7±26.9对83.5±21.6%；p = 0.10）和钳夹期间甘油的脂肪分解率（59.4±22.1%对61.2±14.4%；p = 0.67）均无显著变化。在一项针对无肢端肥大症的非糖尿病胰岛素抵抗参与者的小型II期初步研究中，用培维索孟阻断生长激素受体4周对胰岛素/葡萄糖代谢无显著影响。
