EVIDENCE AGAINST ALTERED EXPRESSION OF GLUT1 OR GLUT4 IN SKELETAL-MUSCLE OF PATIENTS WITH OBESITY OR NIDDM
EVIDENCE AGAINST ALTERED EXPRESSION OF GLUT1 OR GLUT4 IN SKELETAL-MUSCLE OF PATIENTS WITH OBESITY OR NIDDM
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DOI：
10.2337/diabetes.39.7.865
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发表时间：
1990-07-01
期刊：
影响因子：
7.7
通讯作者：
KAHN, BB
中科院分区：
文献类型：
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作者：
PEDERSEN, O;BAK, JF;KAHN, BB
在啮齿动物中由β-细胞毒素链佐星已经表明，这些动物外周组织（肌肉和脂肪）的胰岛素抵抗葡萄糖转运可以部分归因于这些组织中主要胰岛素敏感葡萄糖转运蛋白（GLUT 4）的翻译前减少。由于非胰岛素依赖型糖尿病（NIDDM）的中心特征是胰岛素增强骨骼肌中葡萄糖处理的能力受损，我们检验了GLUT 4表达减少是NIDDM受试者骨骼肌中特征性发现的假设。骨骼肌活检获得17例NIDDM和10瘦和9肥胖非糖尿病受试者。在糖尿病受试者中，7例为新诊断且未经治疗。与年龄和体重相匹配的健康对照组相比，北方印迹和狭缝印迹显示的GLUT 4 mRNA水平或免疫印迹肌膜测定的GLUT 4蛋白没有显著变化。GLUT 4 mRNA和蛋白浓度均与血糖控制程度、空腹血浆胰岛素或血糖、糖尿病病程、体重指数、性别或年龄无关。GLUT 1 mRNA和蛋白水平在糖尿病患者和对照组之间也没有显著差异。因此，与链脲佐菌素诱导的啮齿类动物糖尿病不同，没有证据表明主要胰岛素反应性葡萄糖转运蛋白的表达受损是这些瘦型和中度肥胖NIDDM患者骨骼肌中胰岛素抵抗葡萄糖转运的原因。
Studies of experimental diabetes in rodents induced by the .beta.-cell toxin streptozocin have shown that the insulin-resistent glucose transport of peripheral tissues (muscle and adipose) in these animals can be ascribed in part to a pretranslational reduction of the major insulin-sensitive glucose transporter (GLUT4) in these tissues. Because of central feature of non-insulin-dependent diabetes mellitus (NIDDM) is an impaired ability of insulin to enhance glucose disposal in skeletal muscle, we examined the hypothesis that reduced expression of GLUT4 is a characteristic finding in the skeletal muscle of subjects with NIDDM. Biopsies of skeletal muscles were obtained from 17 patients with NIDDM and 10 lean and 9 obese nondiabetic subjects. Among the diabetic subjects, 7 were newly diagnosed and untreated. Compared with age-matched and body-weight-matched healthy control subjects, there was no significant alteration in the level of GLUT4 mRNA demonstrated by Northern blot and slot blot or GLUT4 protein determined by immunoblotting muscle membranes. Neither GLUT4 mRNA nor protein concentration correlated with the degree of glycemic control, fasting plasma insulin or glucose, diabetes duration, body mass index, sex, or age. GLUT1 mRNA and protein levels were also not significantly different between diabetic and matched control subjects. Thus, unlike streptozocin-induced diabetes in rodents, there is no evidence that impaired expression of the major insulin-responsive glucose transporter is responsible for insulin-resistant glucose transport in the skeletal muscle of these lean and moderately obese NIDDM patients.