Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women
Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women
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DOI：
10.1371/journal.pone.0154119
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发表时间：
2016-04-25
期刊：
影响因子：
3.7
通讯作者：
Bisbal, Catherine
中科院分区：
文献类型：
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作者：
Amouzou, Cacylde;Breuker, Cyril;Bisbal, Catherine
肥胖与胰岛素抵抗（IR）有关，IR是2型糖尿病的主要特征。虽然慢性低度炎症已被确定为IR发展的中枢效应器，在以胰岛素敏感性为特征的肥胖人群中，它从未同时在全身水平和局部骨骼肌和脂肪组织中进行过研究。方法选择30例绝经后正常体重、胰岛素敏感性正常的妇女，随机分为正常体重组、肥胖组、胰岛素敏感性正常组和肥胖组。（对照，CT）和肥胖（I级）胰岛素敏感（OIS）或胰岛素抵抗（OIR），根据他们的体重指数和IR指数的稳态模型评估。他们接受了高胰岛素-正葡萄糖钳夹、血液采样、骨骼肌和皮下脂肪组织活检、活动问卷调查和自我管理的饮食回忆。我们分析了全身水平的胰岛素敏感性、炎症和IR相关参数。在组织中，胰岛素反应进行了评估，由P-Akt/Akt的表达和炎症巨噬细胞浸润以及细胞因子和I κ B α expression.ResultsSystemic水平的脂质，脂肪因子，炎性细胞因子和脂多糖OIS和OIR受试者之间是相等的。在皮下脂肪组织中，抗炎巨噬细胞的数量在OIR中高于CT和OIS，并且与较高的IL-6水平相关。胰岛素诱导Akt磷酸化在CT、OIS和OIR中的程度相同。在骨骼肌中，我们不能检测到任何炎症，即使I κ B α表达在OIR中低于CT。然而，虽然P-Akt/Akt水平增加胰岛素刺激后，在CT和OIS，它保持不变OIR.ConclusionOur结果表明，全身IR发生没有任何变化，全身和组织炎症。我们确定了胰岛素反应的肌肉缺陷是I级肥胖绝经后妇女IR发展的早期机制。
ContextObesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.ObjectivesWe compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.Methods30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and I kappa B alpha expression.ResultsSystemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though I kappa B alpha expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.ConclusionOur results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.