Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance
Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance
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DOI：
10.2337/diabetes.51.4.1102
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Koranyi, L
中科院分区：
文献类型：
--
作者：
Kurucz, I;Morva, A;Koranyi, L
氧化应激被认为在糖尿病及其并发症的发病机制中起作用，并且应激蛋白已被证明在体外和体内保护生物体免受氧化应激。为了研究最丰富的细胞保护应激蛋白之一，诱导型细胞质72-kDa-质量热休克蛋白（Hsp-72）在糖尿病发病机制中的假定作用，我们测量了6名2型糖尿病患者和6名健康对照者肌肉活检组织中的mRNA浓度，（方案1）以及12对2型糖尿病不一致的双胞胎和12名对照受试者接受正常血糖-高胰岛素钳夹联合间接热量测定（方案2）。2型糖尿病患者肌肉组织中Hsp-72 mRNA表达量显著低于健康对照组（在方案1中：5.2 +/- 2.2 vs. 53 +/- 32百万个Hsp-72 mRNA拷贝/μ g总RNA，n = 6，P = 0.0039;在方案2中：3.2 +/- 3.3 vs. 43 +/- 31百万拷贝Hsp-72 mRNA/μ g总RNA，n = 12，P = 0.0001）。与健康对照受试者相比，非糖尿病双胞胎中的Hsp-72 mRNA水平也显著降低（5.8 +/- 5.0 vs. 43 +/- 31，n = 12，P = 0.0001），但当比较两对之间的差异时，它们与糖尿病双胞胎之间也存在统计学显著差异（P = 0.0280）。受检患者肌肉中热休克蛋白mRNA含量与葡萄糖吸收率以及胰岛素刺激的碳水化合物和脂质代谢的其他指标相关。总之，发现2型糖尿病患者骨骼肌中Hsp-72 mRNA水平降低及其与胰岛素抵抗的关系提出了一个问题，即热休克蛋白是否参与2型糖尿病骨骼肌胰岛素抵抗的发病机制。
Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications, and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. To study the putative role of one of the most abundant cytoprotective stress proteins, inducible cytoplasmic 72-kDa-mass heat shock protein (Hsp-72), in the pathogenesis of diabetes, we measured its mRNA concentration in muscle biopsies from six type 2 diabetic patients and six healthy control subjects (protocol 1) as well as in 12 twin pairs discordant for type 2 diabetes and 12 control subjects undergoing a euglycemic-hyperinsulinemic clamp in combination with indirect calorimetry (protocol 2). The amount of Hsp-72 mRNA in muscle was significantly lower in type 2 diabetic patients than in healthy control subjects (in protocol 1: 5.2 +/- 2.2 vs. 53 +/- 32 million copies of Hsp-72 mRNA/mug total RNA, n = 6, P = 0.0039; in protocol 2: 3.2 +/- 3.3 vs. 43 +/- 31 million copies of Hsp-72 mRNA/mug total RNA, n = 12, P = 0.0001). Hsp-72 mRNA levels were also markedly reduced in the nondiabetic co-twins compared with healthy control subjects (5.8 +/- 5.0 vs. 43 +/- 31, n = 12, P = 0.0001), but they were also statistically significantly different from their diabetic co-twins when the difference between the pairs was compared (P = 0.0280). Heat shock protein mRNA content in muscle of examined patients correlated with the rate of glucose uptake and other measures of insulin-stimulated carbohydrate and lipid metabolism. In conclusion, the finding of decreased levels of Hsp-72 mRNA in skeletal muscle of patients with type 2 diabetes and its relationship with insulin resistance raises the question of whether heat shock proteins are involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetes.