Expression profile-dependent improvement of insulin sensitivity by gene delivery of interleukin-6 in a mouse model of type II diabetes.
Expression profile-dependent improvement of insulin sensitivity by gene delivery of interleukin-6 in a mouse model of type II diabetes.
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DOI：
10.1021/mp400288e
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发表时间：
2013-09
影响因子：
4.9
通讯作者：
H. Mukumoto;Yuki Takahashi;M. Ando;M. Nishikawa;Y. Takakura
中科院分区：
文献类型：
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作者：
H. Mukumoto;Yuki Takahashi;M. Ando;M. Nishikawa;Y. Takakura
II型糖尿病是最有问题的代谢紊乱之一，并与继发性疾病如心脏病和眼部并发症有关。白细胞介素6（IL-6）是一种多功能细胞因子，可影响糖尿病患者的糖代谢改变，如胰岛素抵抗。然而，关于IL-6对葡萄糖代谢的作用尚未达成共识。本研究的目的是研究IL-6的表达是否影响饮食诱导的肥胖（DIO）小鼠，II型糖尿病和肥胖症的模型，使用IL-6的基因递送的葡萄糖代谢。DIO小鼠接受流体动力学或肌肉注射IL-6表达质粒以研究IL-6表达位点的重要性。接受持续IL-6基因转移的DIO小鼠在葡萄糖耐量试验中显示出与瘦小鼠相似的葡萄糖水平。IL-6基因转移后，DIO小鼠表现出食物摄入量减少、体重和附睾脂肪重量降低。IL-6基因传递降低了DIO小鼠肝脏、骨骼肌和脂肪组织中代谢相关基因的mRNA表达。接受肌内注射的DIO小鼠的代谢状态略好于接受流体动力学注射的DIO小鼠。观察到炎性细胞浸润到IL-6表达质粒DNA递送的部位。IL-6的瞬时表达对所有检测参数的影响有限。提示IL-6的表达对糖尿病小鼠的肥胖及糖脂代谢有影响，IL-6的表达部位不是影响肥胖的重要因素。
Type II diabetes is one of the most problematic metabolic disorders and is associated with secondary conditions such as heart disease and eye complications. Interleukin-6 (IL-6), a multifunctional cytokine, could influence conditions of altered glucose metabolism such as insulin resistance in diabetic patients. However, a consensus about the role of IL-6 on glucose metabolism has not been reached. The aim of the present study is to investigate whether the expression of IL-6 affects glucose metabolism in diet-induced obesity (DIO) mice, a model of type II diabetes and obesity, using gene delivery of IL-6. DIO mice received hydrodynamic or intramuscular injection of IL-6-expressing plasmid to investigate the importance of the site of IL-6 expression. DIO mice that received a sustained IL-6 gene transfer showed similar glucose levels to lean mice in a glucose tolerance test. DIO mice exhibited reduced food intake and low body and epididymal fat weights after IL-6 gene transfer. IL-6 gene delivery reduced the mRNA expression of metabolism-related genes in the liver, skeletal muscle, and adipose tissue of DIO mice. The metabolic status of DIO mice receiving intramuscular injections was moderately better than that of DIO mice receiving hydrodynamic injections. The infiltration of inflammatory cells into the sites where the IL-6-expressing plasmid DNA was delivered was observed. Transient expression of IL-6 had limited effects on all parameters examined. These results indicate that the expression of IL-6 has an effect on obesity and the metabolism of glucose and lipid in diabetic mice and that the expression site of IL-6 is not an important factor.