The role of adipokines in skeletal muscle inflammation and insulin sensitivity.
The role of adipokines in skeletal muscle inflammation and insulin sensitivity.
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DOI：
10.1186/s12950-018-0185-8
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Jones SW
中科院分区：
文献类型：
--
作者：
Nicholson T;Church C;Baker DJ;Jones SW
目前有一个尚未得到满足的临床需求，即开发更好的药物治疗来改善伴有肥胖的II型糖尿病患者的血糖处理。为此，确定肥胖相关脂肪因子对骨骼肌胰岛素敏感性的影响已成为药物发现研究的一个重要领域。本文综述了脂肪因子在骨骼肌胰岛素信号转导中的功能作用，重点介绍了几种研究较少的新型脂肪因子，并对未来的研究方向进行了展望。脂肪因子瘦素、抵抗素、内脂素和脂联素都被证明通过影响胰岛素信号通路中成分的活性、影响GLUT4转位和调节胰岛素介导的骨骼肌葡萄糖摄取来影响骨骼肌的胰岛素敏感性。此外，对脂肪组织分泌组的蛋白质组学分析最近发现了几种新的脂肪因子，包括vaspin、趋化蛋白和pref-1，它们与人类肥胖和胰岛素抵抗有关，并在功能上影响胰岛素信号通路。然而，这些功能发现主要是在啮齿动物身上研究的结果，体外研究使用了大鼠L6或小鼠C2C12成肌细胞和/或肌管。尽管分离和培养人成肌细胞并将其分化为肌管的方法学已经建立，但利用人类肌肉体外模型来验证脂肪因子对骨骼肌胰岛素敏感性的功能验证是有限的。了解脂肪因子在骨骼肌中调节胰岛素敏感性的作用和功能，可能有助于开发治疗2型糖尿病的新疗法。然而，到目前为止，在人类骨骼肌细胞和组织中进行的研究有限。这种人类体外研究应该优先考虑，以减少候选药物在临床上失败的风险，因为假设啮齿动物骨骼肌靶向验证研究将转化为人类。
There is currently an unmet clinical need to develop better pharmacological treatments to improve glucose handling in Type II Diabetes patients with obesity. To this end, determining the effect of obesity-associated adipokines on skeletal muscle insulin sensitivity has emerged as an important area of drug discovery research. This review draws together the data on the functional role of adipokines on skeletal muscle insulin signalling, highlights several understudied novel adipokines and provides a perspective on the direction of future research. The adipokines leptin, resistin, visfatin and adiponectin have all been shown to affect skeletal muscle insulin sensitivity by impacting on the activity of components within insulin signalling pathways, affecting GLUT4 translocation and modulating insulin-mediated skeletal muscle glucose uptake. Furthermore, proteomic analysis of the adipose tissue secretome has recently identified several novel adipokines including vaspin, chemerin and pref-1 that are associated with obesity and insulin resistance in humans and functionally impact on insulin signalling pathways. However, predominantly, these functional findings are the result of studies in rodents, with in vitro studies utilising either rat L6 or murine C2C12 myoblasts and/or myotubes. Despite the methodology to isolate and culture human myoblasts and to differentiate them into myotubes being established, the use of human muscle in vitro models for the functional validation of adipokines on skeletal muscle insulin sensitivity is limited. Understanding the mechanism of action and function of adipokines in mediating insulin sensitivity in skeletal muscle may lead to the development of novel therapeutics for patients with type 2 diabetes. However, to date, studies conducted in human skeletal muscle cells and tissues are limited. Such human in vitro studies should be prioritised in order to reduce the risk of candidate drugs failing in the clinic due to the assumption that rodent skeletal muscle target validation studies will to translate to human.
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DOI：
10.15386/cjm.2014.8872.871.afc1
发表时间：
2014
期刊：
Clujul medical (1957)
影响因子：
--
作者：
Cătoi AF;Suciu Ş;Pârvu AE;Copăescu C;Galea RF;Buzoianu AD;Vereşiu IA;Cătoi C;Pop ID
通讯作者：
Pop ID
FA1诱导通过瘦，肥胖和2型糖尿病患者建立的人肌管中的促炎和抗辅助途径/标记，但不胰岛素抵抗。
影响因子：
5.2
作者：
Abdallah BM;Beck-Nielsen H;Gaster M
通讯作者：
Gaster M
DOI：
10.1136/bmj.c2181
发表时间：
2010-05-20
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
de Jager J;Kooy A;Lehert P;Wulffelé MG;van der Kolk J;Bets D;Verburg J;Donker AJ;Stehouwer CD
通讯作者：
Stehouwer CD
影响因子：
4.8
作者：
Deng W;Li C;Zhang Y;Zhao J;Yang M;Tian M;Li L;Zheng Y;Chen B;Yang G
通讯作者：
Yang G
影响因子：
2.2
作者：
Bates, SH;Gardiner, JV;Bailey, CJ
通讯作者：
Bailey, CJ