Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes.

Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes.
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DOI:
10.1371/journal.pone.0158209
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Henry RR
Henry RR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ciaraldi TP;Ryan AJ;Mudaliar SR;Henry RR

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骨骼肌分泌称为肌因子的因子。我们采用从2型糖尿病(T2 D)和非糖尿病(ND)受试者培养的分化的人骨骼肌细胞(hSMC)来研究T2 D对肌因子分泌的影响。培养24小时后,确定所选肌因子的浓度范围超过4个数量级。与ND肌管相比,T2 D hSMC释放增加量的IL 6、IL 8、IL 15、TNFa、生长相关癌基因(GRO)a、单核细胞趋化蛋白(MCP)-1和卵泡抑素。T2 D和ND hSMC分泌相似水平的IL 1 β和血管内皮生长因子(VEGF)。用炎症因子脂多糖(LPS)或棕榈酸酯治疗增加了许多肌因子的分泌,包括:GRO α、IL 6、IL 8、IL 15和TNF α,但不一致地改变IkBa、p44/42 MAPK、p38 MAPK、c-Jun N-末端激酶(JNK)和NF-κ B的蛋白含量和/或磷酸化,也不导致基础和胰岛素刺激的葡萄糖摄取或游离脂肪酸氧化的一致变化。相反,吡格列酮或油酸酯治疗导致几种肌因子分泌适度减少。我们的研究结果表明,改变分泌的一些肌因子是一个内在的属性的骨骼肌在T2 D,这表明一个假定的作用肌因子在骨骼肌的响应T2 D。
Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D.