Peripheral effects of nesfatin-1 on glucose homeostasis.
Peripheral effects of nesfatin-1 on glucose homeostasis.
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Nesfatin-1 对血糖稳态的外周影响
DOI：
10.1371/journal.pone.0071513
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Li Z;Gao L;Tang H;Yin Y;Xiang X;Li Y;Zhao J;Mulholland M;Zhang W
目的/假设外周给药nesfatin-1对葡萄糖稳态的作用仍然存在争议。本研究的目的是表征外周nesfatin-1调节葡萄糖代谢的机制。方法通过渗透泵持续输注nesfatin-1对小鼠糖代谢的影响。Western blotting和免疫荧光染色检测AKT磷酸化和Glut 4的变化。从雄性小鼠中分离原代肌细胞、脂肪细胞和肝细胞。结果外周持续输注nesfatin-1可改变正常或高脂饮食小鼠的糖耐量和胰岛素敏感性，而中枢注射nesfatin-1则无影响。在体内和体外培养的min 6细胞中，Nesfatin-1增加胰岛素分泌。此外，nesfatin-1上调胰腺和min 6胰岛细胞中AKT的磷酸化。在喂食正常饮食的小鼠中，外周nesfatin-1显著增加骨骼肌、脂肪组织和肝脏中胰岛素刺激的AKT磷酸化;在喂食高脂饮食的小鼠中，在骨骼肌和脂肪组织中观察到类似的作用。在基础条件下和胰岛素刺激后，外周nesfatin-1显着增加GLUT 4在骨骼肌和脂肪组织中的膜转位在小鼠喂养的饮食。体外研究表明，nesfatin-1增加来自骨骼肌，脂肪组织和肝脏的细胞中AKT磷酸化的基础和胰岛素刺激水平。结论nesfatin-1通过改变骨骼肌、脂肪组织和肝脏中AKT磷酸化和GLUT 4膜转位，增加胰岛素分泌和胰岛素敏感性，从而改变葡萄糖代谢。
Aims/hypothesis The actions of peripherally administered nesfatin-1 on glucose homeostasis remain controversial. The aim of this study was to characterize the mechanisms by which peripheral nesfatin-1 regulates glucose metabolism. Methods The effects of nesfatin-1 on glucose metabolism were examined in mice by continuous infusion of the peptide via osmotic pumps. Changes in AKT phosphorylation and Glut4 were investigated by Western blotting and immnuofluorescent staining. Primary myocytes, adipocytes and hepatocytes were isolated from male mice. Results Continuous peripheral infusion of nesfatin-1 altered glucose tolerance and insulin sensitivity in mice fed either normal or high fat diet, while central administration of nesfatin-1 demonstrated no effect. Nesfatin-1 increases insulin secretion in vivo, and in vitro in cultured min6 cells. In addition, nesfatin-1 up-regulates the phosphorylation of AKT in pancreas and min6 islet cells. In mice fed normal diet, peripheral nesfatin-1 significantly increased insulin-stimulated phosphorylation of AKT in skeletal muscle, adipose tissue and liver; similar effects were observed in skeletal muscle and adipose tissue in mice fed high fat diet. At basal conditions and after insulin stimulation, peripheral nesfatin-1 markedly increased GLUT4 membrane translocation in skeletal muscle and adipose tissue in mice fed either diet. In vitro studies showed that nesfatin-1 increased both basal and insulin-stimulated levels of AKT phosphorylation in cells derived from skeletal muscle, adipose tissue and liver. Conclusions Our studies demonstrate that nesfatin-1 alters glucose metabolism by mechanisms which increase insulin secretion and insulin sensitivity via altering AKT phosphorylation and GLUT 4 membrane translocation in the skeletal muscle, adipose tissue and liver.
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