Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects
Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects
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DOI：
10.1056/nejmoa054862
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发表时间：
2006-06-15
影响因子：
158.5
通讯作者：
Kahn, Barbara B.
中科院分区：
文献类型：
--
作者：
Graham, Timothy E.;Yang, Qin;Kahn, Barbara B.
背景：胰岛素抵抗在2型糖尿病中具有因果关系。在胰岛素抵抗状态下，血清中视黄醇结合蛋白4（RBP4）（一种由脂肪细胞分泌的蛋白质）水平升高。小鼠实验表明，RBP4水平升高会导致胰岛素抵抗。我们试图确定血清RBP4水平是否与胰岛素抵抗相关，以及在改善胰岛素敏感性的干预后的变化。我们还确定了血清RBP4水平升高是否与葡萄糖转运蛋白4（GLUT4）在脂肪细胞，胰岛素抵抗的早期病理特征的表达减少相关。方法：我们测定了血清RBP4，胰岛素抵抗，代谢综合征的三组受试者的组成部分。一组在运动训练后重复测量。GLUT4蛋白在分离的脂肪cells.RESULTS：血清RBP4水平与肥胖，糖耐量受损，或2型糖尿病和非肥胖，非糖尿病受试者与2型糖尿病家族史的胰岛素抵抗的幅度相关。血清RBP4升高与代谢综合征的组成部分相关，包括体重指数增加，腰臀比，血清甘油三酯水平，收缩压和高密度脂蛋白胆固醇水平降低。只有在胰岛素抵抗改善的受试者中，运动训练与血清RBP4水平降低相关。脂肪细胞GLUT4蛋白和血清RBP4水平呈负相关.CONCLUSIONS：RBP4是一种脂肪细胞分泌的分子，在血清中升高之前，坦率的糖尿病的发展，并出现确定胰岛素抵抗和相关的心血管危险因素的主题与不同的临床表现。这些发现为旨在降低血清RBP4水平的抗糖尿病治疗提供了理论基础。
BACKGROUND:Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance.METHODS:We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes.RESULTS:Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated.CONCLUSIONS:RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels.