Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects
Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects
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DOI：
10.2337/diabetes.51.1.30
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发表时间：
2002-01-01
期刊：
影响因子：
7.7
通讯作者：
Henry, RR
中科院分区：
文献类型：
--
作者：
Ciaraldi, TP;Kong, APS;Henry, RR
格列本脲治疗失败的2型糖尿病受试者随机接受二甲双胍（2，550 mg/天）或曲格列酮（600 mg/天）的额外治疗3-4个月。治疗前后分别取腹部皮下脂肪组织进行活检。两种处理的甘草酸控制相似。二甲双胍治疗使胰岛素刺激的全身葡萄糖处置率增加20%（P < 0.05）;曲格列酮的反应更大（增加44%，与基线相比P < 0.01，与二甲双胍相比P < 0.05）。接受曲格列酮治疗的受试者表现出体重增加（5 ± 2 kg，P < 0.05）、脂肪细胞大小增加和血清瘦素水平升高的趋势。二甲双胍治疗的受试者体重稳定，瘦素水平不变，脂肪细胞大小减少（至对照组的84 ± 4%，P < 0.005）。二甲双胍治疗受试者的分离脂肪细胞中的葡萄糖转运与治疗前相比没有变化。曲格列酮治疗后，无胰岛素（Rx前的321 +/- 134%，P < 0.05）和有胰岛素（418 +/-161%，P < 0.05）的葡萄糖转运均升高。二甲双胍处理对脂肪细胞中GLUT 1或GLUT 4蛋白的含量没有影响。曲格列酮治疗后，GLUT 4蛋白表达增加两倍（202 +/-42%，P < 0.05）。胰岛素刺激的Akt丝氨酸磷酸化在曲格列酮治疗后增加（Rx前反应的170 +/- 34%，P < 0.05），二甲双胍治疗后无变化。我们得出结论，曲格列酮上调脂肪细胞葡萄糖转运、GLUT 4表达和胰岛素信号传导的能力有助于其对全身葡萄糖处置的更大影响。
Type 2 diabetic subjects failing glyburide therapy were randomized to receive additional therapy with either metformin (2,550 mg/day) or troglitazone (600 mg/day) for 3-4 months. Biopsies of subcutaneous abdominal adipose tissue were obtained before and after therapy. Glycemic control was similar with both treatments. Metformin treatment increased insulin-stimulated whole-body glucose disposal rates by 20% (P < 0.05); the response to troglitazone was greater (44% increase, P < 0.01 vs. baseline, P < 0.05 vs. metformin). Troglitazone-treated subjects displayed a tendency toward weight gain (5 +/- 2 kg, P < 0.05), increased adipocyte size, and increased serum leptin levels. Metformin-treated subjects were weight-stable, with unchanged leptin levels and reduced adipocyte size (to 84 +/- 4% of control, P < 0.005). Glucose transport in isolated adipocytes from metformin-treated subjects was unaltered from pretreatment. Glucose transport in both the absence (321 +/- 134% of pre-Rx, P < 0.05) and presence of insulin (418 +/- 161%, P < 0.05) was elevated after troglitazone treatment. Metformin treatment had no effect on adipocyte content of GLUT1 or GLUT4 proteins. After troglitazone treatment, GLUT4 protein expression was increased twofold (202 +/- 42%, P < 0.05). Insulin-stimulated serine phosphorylation of Akt was augmented after troglitazone (170 +/- 34% of pre-Rx response, P < 0.05) treatment and unchanged by metformin. We conclude that the ability of troglitazone to upregulate adipocyte glucose transport, GLUT4 expression, and insulin signaling can contribute to its greater effect on whole-body glucose disposal.