抗阻训练改善骨骼肌胰岛素抵抗的新机制-肌细胞微环境的改善

Skeletal muscle insulin resistance (IR) is critical to the development and progression of type II diabetes mellitus (T2DM). Resistance exercise training, traditionally only used in inducing muscle growth, has recently been found to be able to improve muscle IR. However, the mechanism for this improvement is still unknown. Our previous study on skeletal muscle transcriptomics indicated that ECM remodeling plays a key role in muscle adaptation to resistance exercise training, and recent studies have also demonstrated that negative alterations occurring in skeletal muscle ECM contribute significantly to IR. Therefore, we hypothesize that resistance exercise training can reverse the ECM changes that occurre during IR development and thereby improve IR. In the proposed study, we will 1) use T2DM mouse model to examine changes in key components of the ECM following resistance exercise training in mice, and analyze the association between changes in ECM and IR; 2) use decellularized muscle ECM to prepare coatings for cell culture in order to analyze the influence of the altered status of the ECM on the ability of L6 cell in glucose absorption to establish the relationship between resistance exercise, ECM remodeling and IR. This study will help improve our understanding of resistance exercise as a useful directive for T2DM prevention and treatment, so that optimization of exercise programing in disease control can be achieved. In addition, this study will guide the development of new strategies in T2DM prevention and treatment.

骨骼肌胰岛素抵抗(IR)是糖尿病（T2DM）发生和发展的关键。抗阻训练是促进肌肉增长的传统运动方式，最近研究发现它可以改善骨骼肌IR，但作用机制还不明了。我们前期基因组学的研究结果表明细胞外基质（ECM）重塑是抗阻训练中肌肉适应性反应的关键环节，而最新研究表明ECM性变与骨骼肌IR发病直接相关。因此，我们提出假设：抗阻训练可以纠正骨骼肌IR发病过程中ECM的性变，从而改善骨骼肌IR。在项目中，我们将1）利用大鼠ＩＲ模型，深入地分析负重爬梯（抗阻训练）训练后骨骼肌ECM的性状改变及其与胰岛素敏感性的相关性；2）用脱细胞后的骨骼肌ECM培养L6肌细胞，比较不同状态的ECM对L6细胞胰岛素作用下葡萄糖摄取量的影响，从而确立抗阻训练、ECM性变和IR的相互关系。本研究将对充分了解抗阻训练预防T2DM的机制和潜能，从而为优化T2DM运动预防和治疗做出贡献；并为研发新的T2DM防治手段提供新的思路

骨骼肌胰岛素抵抗(IR)是糖尿病（T2DM）发生和发展的关键。抗阻训练是促进肌肉增长的传统运动方式，最近研究发现它可以改善骨骼肌IR，但作用机制还不明了。我们前期基因组学的研究结果表明细胞外基质（ECM）重塑是抗阻训练中肌肉适应性反应的关键环节，而最新研究表明ECM性变与骨骼肌IR发病直接相关。因此，我们提出假设：抗阻训练可以纠正骨骼肌IR发病过程中ECM的性变，从而改善骨骼肌IR。在项目中，我们1）利用大鼠IR模型，深入地分析了负重爬梯（抗阻训练）训练后骨骼肌ECM的性状改变及其与胰岛素敏感性的相关性；2）用脱细胞后的骨骼肌ECM培养L6肌细胞，比较了不同状态的ECM对L6细胞胰岛素作用下葡萄糖摄取量的影响。本研究确立了骨骼肌ECM与胰岛素抵抗发生和发展的相关性，从而为胰岛素抵抗机理的进一步认识做出了贡献；本研究通过动物实验确立了抗阻训练对抗高脂膳食引发的胰岛素抵抗的有效性，为抗阻训练在糖尿病预防和治疗中的应用提供了理论依据；另外本研究成功建立了负重爬梯大鼠抗阻训练模型，该模型为今后抗阻训练相关研究动物造模提供成功范例；最后我们尝试了用脱细胞ECM进行细胞干预，该实验技术在细胞微环境研究领域有一定的应用价值。