Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects
Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects
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DOI：
10.1111/j.1463-1326.2007.00801.x
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发表时间：
2008-09-01
影响因子：
5.8
通讯作者：
Kawamori, R.
中科院分区：
文献类型：
--
作者：
Tamura, Y.;Watada, H.;Kawamori, R.
目的：近年来的研究表明，胰岛素抵抗与肝内脂质（IHL）和肌内脂质（IMCL）含量增加有关。虽然二甲双胍主要改善肝脏的胰岛素抵抗，但其对IHL和IMCL的影响尚未阐明。本研究的目的是研究低剂量二甲双胍的作用（750 mg/天）对外周胰岛素敏感性、IHL和IMCL的影响。在低剂量二甲双胍治疗前和治疗后3个月，对8名超重/肥胖日本受试者[体重指数（BMI）> 25 kg/m2]进行了血液采样研究，通过（1）H磁共振波谱和正常血-高胰岛素钳夹期间葡萄糖输注速率（GIR）测量IHL和IMCL，作为外周胰岛素敏感性的指标。3个月的低剂量二甲双胍治疗没有改变体重、全身脂肪、脂肪分布或体力活动水平，但GIR增加了31%（从6.24 +/- 0.86至7.82 +/- 0.82 mg/kg/min，p < 0.01）。尽管二甲双胍治疗未改变IMCL（从4.1 +/- 1.0到4.2 +/- 0.9，不显著），IHL降低21%（从15.9 +/- 2.8到11.8 +/-2.2%，p < 0.05）。低剂量二甲双胍治疗3个月可改善外周胰岛素敏感性并降低IHL，而不会显著改变BMI、肥胖或IMCL。
Aim: Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL.Methods: Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) > 25 kg/m(2)] were studied with blood sampling, measurement of IHL and IMCL by (1)H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic-hyperinsulinaemic clamp as an index of peripheral insulin sensitivity.Results: A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 +/- 0.86 to 7.82 +/- 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 +/- 1.0 to 4.2 +/- 0.9, not significant), it decreased IHL by 21% (from 15.9 +/- 2.8 to 11.8 +/- 2.2%, p < 0.05).Conclusions: A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.