IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle
IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle
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DOI：
10.1096/fj.201600832r
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发表时间：
2017-02-01
期刊：
影响因子：
4.8
通讯作者：
Kim, Jason K.
中科院分区：
文献类型：
--
作者：
Dagdeviren, Sezin;Jung, Dae Young;Kim, Jason K.
能量平衡改变和胰岛素抵抗是衰老的重要特征。骨骼肌是葡萄糖代谢的主要场所，衰老相关炎症在骨骼肌胰岛素抵抗中的作用尚不清楚。为了进行研究，我们检测了18月龄的肌肉特异性过表达IL-10（M-IL 10）的转基因小鼠和野生型小鼠在高胰岛素-正常血糖钳夹过程中的葡萄糖代谢。尽管脂肪量和能量平衡相似，但与年龄匹配的WT小鼠相比，M-IL 10小鼠受到保护，免受衰老相关的胰岛素抵抗，葡萄糖输注速率、全身葡萄糖周转和骨骼肌葡萄糖摄取显著增加（类似于60%; P < 0.05）。这种保护作用与肌肉炎症减少有关，但在衰老的M-IL 10小鼠中脂肪组织炎症没有变化。这些结果表明骨骼肌炎症在衰老介导的胰岛素抵抗中的重要性，我们的研究结果进一步暗示了抗炎细胞因子在治疗衰老介导的胰岛素抵抗中的潜在治疗作用。
Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (M-IL10) and in wild-type mice during hyperinsulinemic-euglycemic clamping. Despite similar fat mass and energy balance, M-IL10 mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (similar to 60%; P < 0.05), as compared to age-matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging M-IL10 mice. These results demonstrate the importance of skeletal muscle inflammation in aging-mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti-inflammatory cytokine in the treatment of aging-mediated insulin resistance.