Table_7_Differences in protein expression, at the basal state and at 2 h of insulin infusion, in muscle biopsies from healthy Arab men with high or low insulin sensitivity measured by hyperinsulinemic euglycemic clamp.xlsx

BackgroundSkeletal muscle is the main site for insulin-dependent glucose disposal. The hyperinsulinemic euglycemic clamp (HIEC) is the gold standard for the assessment of insulin sensitivity (IS). We have previously shown that insulin sensitivity, measured by HIEC, varied widely among a group of 60 young healthy men with normoglycemia. The aim of this study was to correlate the proteomic profile of skeletal muscles to insulin sensitivity.MethodsMuscle biopsies from 16 subjects having the highest (M ≥ 13; n = 8, HIS) and lowest (M ¾ 6, n = 8, LIS) IS were obtained at baseline and during insulin infusion after stabilization of the blood glucose level and glucose infusion rate at the end of the HIEC. The samples were processed using a quantitative proteomic analysis approach.ResultsAt baseline, 924 proteins were identified in the HIS and LIS groups. Among the 924 proteins detected in both groups, three were suppressed and three were increased significantly in the LIS subjects compared with the HIS subjects. Following insulin infusion, 835 proteins were detected in both groups. Among the 835 proteins, two showed differential responsiveness to insulin; ATP5F1 protein was decreased, and MYLK2 was higher in the LIS group compared with that in the HIS group. Our data suggest that alteration in mitochondrial proteins and an increased number of proteins involved in fast-twitch fiber correlate to insulin sensitivity in healthy young Arab men.ConclusionsThese results suggest a change in a small number of differentially expressed proteins. A possible reason for this small change could be our study cohorts representing a homogeneous and healthy population. Additionally, we show differences in protein levels from skeletal muscle in low and high insulin sensitivity groups. Therefore, these differences may represent early events for the development of insulin resistance, pre-diabetes, and type 2 diabetes.

背景：骨骼肌是胰岛素依赖性葡萄糖处置的主要场所。高胰岛素正常血糖钳夹技术（HIEC）是评估胰岛素敏感性（IS）的黄金标准。我们先前的研究表明，通过HIEC测量的胰岛素敏感性在60名血糖正常的年轻健康男性中存在广泛差异。本研究旨在将骨骼肌的蛋白质组谱与胰岛素敏感性相关联。方法：在HIEC结束时，血葡萄糖水平和葡萄糖输注速率稳定后，从胰岛素敏感性最高（M ≥ 13；n = 8，高胰岛素敏感性组，HIS）和最低（M ≤ 6，n = 8，低胰岛素敏感性组，LIS）的16名受试者中获取了肌肉活检样本。这些样本采用了定量蛋白质组学分析方法进行处理。结果：在基线时，HIS和LIS组中分别鉴定出924种蛋白质。在两组均检测到的924种蛋白质中，与HIS组相比，LIS组中有三种蛋白质显著下调，三种蛋白质显著上调。在胰岛素输注后，两组中均检测到835种蛋白质。在这835种蛋白质中，有两种蛋白质对胰岛素的反应性存在差异；ATP5F1蛋白在LIS组中的含量较HIS组降低，而MYLK2蛋白在LIS组中的含量较HIS组升高。我们的数据表明，线粒体蛋白质的改变以及快速收缩纤维相关蛋白质数量的增加与年轻阿拉伯男性的胰岛素敏感性相关。结论：这些结果表明，少数差异表达蛋白质发生变化。这种微小变化的原因可能是我们的研究队列代表了同质化和健康的群体。此外，我们展示了低胰岛素敏感性和高胰岛素敏感性组骨骼肌蛋白质水平的差异。因此，这些差异可能代表着胰岛素抵抗、前糖尿病和2型糖尿病发展的早期事件。