Resistin and type 2 diabetes: Regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes
Resistin and type 2 diabetes: Regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes
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DOI：
10.1210/jc.2003-030898
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发表时间：
2003-12-01
影响因子：
5.8
通讯作者：
Kumar, S
中科院分区：
文献类型：
--
作者：
McTernan, PG;Fisher, FM;Kumar, S
抵抗素是一种脂肪细胞分泌因子，在啮齿动物模型中被认为与肥胖与2型糖尿病有关，但其与人类糖尿病的相关性仍不确定。虽然先前的研究表明这种脂肪细胞因子作为一种致病因子，但其功能作用、胰岛素的调节以及糖尿病状态下血清抵抗素浓度的改变仍有待阐明。因此，本研究的目的是分析2型糖尿病患者的血清抵抗素浓度；确定胰岛素和罗格列酮（RSG）在体外对抵抗素的调节作用，并检测重组人抵抗素对体外糖脂代谢的功能影响。分析了45例2型糖尿病患者和34例非糖尿病患者的血清抵抗素浓度。将人皮下脂肪细胞与胰岛素、RSG以及胰岛素与RSG联合孵育，观察其对抵抗素分泌的影响。与非糖尿病患者相比，2型糖尿病患者血清抵抗素升高约20% (P = 0.004)，与c反应蛋白相关。在这个队列中，没有其他参数，包括肥胖和空腹胰岛素水平，与血清抵抗素相关。然而，在体外，胰岛素刺激脂肪细胞以浓度依赖的方式分泌抵抗素蛋白[对照组，1215 +/- 87 pg/ml（平均+/- SEM）；胰岛素1 nM， 1414.0 +/- 89 pg/ml；1 muM胰岛素，1797 +/- 107 pg/ml （P < 0.001）。RSG （10 nM）降低胰岛素介导的抵抗素蛋白分泌升高（1 nM胰岛素+ RSG， 971 +/- 35 pg/ml；胰岛素，1 μ M胰岛素+ RSG， 1019 +/- 28 pg/ml， P< 0.01）。10 ng/ml及更高浓度重组抵抗素组小鼠葡萄糖摄取降低（P < 0.05）。我们的体外研究表明，在分化的前脂肪细胞中，人重组抵抗素可以减少少量但显著的葡萄糖摄取。在人腹部sc脂肪细胞中，RSG阻断胰岛素介导的抵抗素分泌释放。总之，糖尿病患者血清抵抗素升高反映了2型糖尿病患者普遍存在的亚临床炎症。我们的体外研究表明抵抗素在减少葡萄糖摄取方面有一定的作用，抑制抵抗素的表达可能有助于噻唑烷二酮类药物的胰岛素增敏和降血糖作用。
Resistin, an adipocyte secreted factor, has been suggested to link obesity with type 2 diabetes in rodent models, but its relevance to human diabetes remains uncertain. Although previous studies have suggested a role for this adipocytokine as a pathogenic factor, its functional effects, regulation by insulin, and alteration of serum resistin concentration by diabetes status remain to be elucidated. Therefore, the aims of this study were to analyze serum resistin concentrations in type 2 diabetic subjects; to determine the in vitro effects of insulin and rosiglitazone (RSG) on the regulation of resistin, and to examine the functional effects of recombinant human resistin on glucose and lipid metabolism in vitro. Serum concentrations of resistin were analyzed in 45 type 2 diabetic subjects and 34 nondiabetic subjects. Subcutaneous human adipocytes were incubated in vitro with insulin, RSG, and insulin in combination with RSG to examine effects on resistin secretion. Serum resistin was increased by approximately 20% in type 2 diabetic subjects compared with nondiabetic subjects ( P = 0.004) correlating with C-reactive protein. No other parameters, including adiposity and fasting insulin levels, correlated with serum resistin in this cohort. However, in vitro, insulin stimulated resistin protein secretion in a concentration-dependent manner in adipocytes [ control, 1215 +/- 87 pg/ml ( mean +/- SEM); 1 nM insulin, 1414.0 +/- 89 pg/ml; 1 muM insulin, 1797 +/- 107 pg/ml ( P < 0.001)]. RSG (10 nM) reduced the insulin-mediated rise in resistin protein secretion (1 nM insulin plus RSG, 971 +/- 35 pg/ml; insulin, 1 mu M insulin plus RSG, 1019 +/- 28 pg/ml; P< 0.01 vs. insulin alone). Glucose uptake was reduced after treatment with 10 ng/ml recombinant resistin and higher concentrations ( P < 0.05). Our in vitro studies demonstrated a small, but significant, reduction in glucose uptake with human recombinant resistin in differentiated preadipocytes. In human abdominal sc adipocytes, RSG blocks the insulin-mediated release of resistin secretion in vitro. In conclusion, elevated serum resistin in human diabetes reflects the subclinical inflammation prevalent in type 2 diabetes. Our in vitro studies suggest a modest effect of resistin in reducing glucose uptake, and suppression of resistin expression may contribute to the insulin-sensitizing and glucose-lowering actions of the thiazolidinediones.