Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: Relationship to glucose disposal

Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: Relationship to glucose disposal
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DOI:
10.1053/meta.2002.50108
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发表时间:
2003-05-01
影响因子:
9.8
通讯作者:
Henry, RR
Henry, RR
中科院分区:
医学1区
文献类型:
--
作者:
Mathieu-Costello, O;Kong, A;Henry, RR

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这项工作的目的是比较不同的抗糖尿病治疗对磺脲类药物治疗失败的2型糖尿病患者骨骼肌表型的影响。受试者在格列本脲的基础上加用噻唑烷二酮(曲格列酮,TGZ)或双胍(二甲双胍,MET)治疗3至4个月。胰岛素的作用是用高胰岛素血症(300 mU(.)M(-2.)M in(-1))正血糖(5.0~5.5 mm ol/L)钳夹。取股外侧肌活检进行形态分析。尽管血糖控制相似,但TGZ治疗后胰岛素刺激的葡萄糖处置速率(GDR)的相对增加(37+/-8%,P<0.05)大于MET治疗后(21+/-11%,P<0.05)。两种处理对肌肉的纤维类型组成均无影响。与非糖尿病组相比,糖尿病患者的毛细血管密度降低(P<.01),经TGZ治疗后毛细血管密度增加(P<.05),而MET无明显效果。糖尿病肌肉也表现出较低的线粒体体积密度,这两种治疗方法都没有改变。TGZ和MET治疗均能降低肌脂含量(以脂滴表示的纤维体积百分比),TGZ的相对降幅更大(MET为-33%,v-23%)。GDR的相对改善(%)与血脂含量变化呈正相关(r=-0.756,P
The goal of this work was to compare the effects of different antidiabetic therapies on the phenotype of skeletal muscle in type 2 diabetic subjects failing sulfonylurea therapy. Subjects were treated with a thiazolidinedione (troglitazone, TGZ) or a biguanide (metformin, MET) in addition to glyburide for 3 to 4 months. Insulin action was determined with a hyperinsulinemic (300 mU (.) m(-2 .) min(-1)) euglycemic (5.0 to 5.5 mmol/L) clamp. Biopsies were obtained from the vastus lateralis muscle for morphological analysis. Despite similar glycemic control, relative increases in the insulin-stimulated glucose disposal rate (GDR) were greater after TGZ treatment (37 +/- 8% increase, P < .05) than after MET (21 +/- 11%, P < .05). Neither treatment had any effect on fiber type composition of the muscle. Capillary density was reduced in diabetic subjects compared to a nondiabetic group (P < .01) and was increased with TGZ treatment (P < .05), while MET was without significant effect. Diabetic muscle also displayed a lower mitochondrial volume density that was unaltered by either treatment. Both TGZ and MET therapy resulted in a reduction in the lipid content of muscle (percent fiber volume as lipid droplets); the relative decrease tended to be greater for TGZ (-33% v -23% for MET). The relative (%) improvement in GDR was correlated with the change in lipid content (r = -0.756, P