基于肠道菌群调控的胰腺GLP-1R受体表达探讨太极拳对2型糖尿病患者降糖机制的研究

Type 2 diabetes mellitus (T2DM) is the third largest health killer worldwide, which has posed a thrilling threat to human health with its high morbidity and low control rate. TCM holds that disorder of spleen and stomach function is the main pathogenesis of T2DM. Our preliminary clinical study found that Tai Chi Chuan exercise, emphasized on the preservation and protection of spleen and stomach, was able to lower the blood glucose on patients with T2DM, and the effect was sustaining. However, the specific mechanism of Tai Chi Chuan for T2DM remains unclear. Recent studies have demonstrated that intestinal flora imbalance is a key factor for T2DM, manifested as down-regulated GLP-1R expression mediated by intestinal dysbacteriosis, resulting in the decrease of insulin secretion of islet β cells, which plays an important role in the onset of T2DM. Therefore, it is critical to treat T2DM by means of normalizing the intestinal dysbacteriosis and up-regulating the expression of GLP-1R, thus bringing the gut back to homeostasis.Exercise can change gut healthy state. Relatively low-intensity physical activity is more conducive to intestinal health. Tai Chi Chuan is a low-intensity aerobic exercise that focuses on the spleen and stomach.Therefore, from the perspective of intestinal flora mediated GLP-1R expression level, our research will select T2DM as research subjects, Tai Chi Chuan exercise as intervention, advanced technology such as metagenomics and molecular imaging will be utilized, aiming to investigate the hypoglycemic effect of Tai Chi Chuan exercise and the infulence of Tai Chi Chuan on intestinal flora mediated GLP-1R expression level, so as to illuminate the hypoglycemic mechanism of Tai Chi Chuan exercise for T2DM, thus providing a scientific basis for the clinical popularization and application of Tai Chi Chuan for advantageous diseases, and promoting the inheritance and development of TCM health rehabilitation exercise.

2型糖尿病（T2DM）是全球第三大健康杀手，其高发病率和低控制率给人类健康带来严重威胁。脾胃功能失调是T2DM的主要病机，前期临床研究发现以顾护脾胃为重点的太极拳对T2DM具有良好疗效，且效应具有一定持续性，但其作用机制尚不明确。最近研究表明肠道菌群失调介导的GLP-1R表达下调，引起胰岛β细胞胰岛素分泌减少，是T2DM发病的重要机制。因此，调节肠道菌群，上调GLP-1R表达，恢复肠道稳态，是治疗T2DM的关键。运动可以改变肠道健康状态，太极拳是一种着重顾护脾胃的低强度有氧运动。因此，本研究从肠道菌群调控的GLP-1R表达水平入手，以T2DM患者为研究对象，太极拳为干预手段，运用宏基因组和分子影像学等先进技术，研究太极拳对肠道菌群调控的GLP-1R表达水平和血糖的影响，以深入阐释太极拳治疗T2DM的降糖机制，为太极拳治疗优势病种的临床推广应用提供科学依据，促进中医养生康复功法的传承与发展。

2型糖尿病（T2DM）是继心脑血管疾病、肿瘤之后全球第三大严重危害人类健康的慢性非传染性疾病。太极拳被广泛运用于糖尿病的防治中，然而其具体机制尚不明确。因此，本研究采用随机对照试验，观察12周太极拳运动对T2DM患者血糖、血脂和生活质量等的干预效果，并与步行运动和等待治疗进行比较，以明确太极拳对T2DM的临床疗效。同时通过宏基因组、影像学和代谢组学等先进技术，研究太极拳对肠道菌群以及GLP-1表达水平的影响，以阐释太极拳治疗T2DM的降糖机制。研究结果表明：太极拳可降低T2DM患者的血糖、提高血清GLP-1水平，改善胰岛功能，同时可提高其生活质量，具有良好的临床疗效。肠菌结果表明，相比于健康受试者，T2DM患者的肠道菌群在门、纲、目、属和种水平均存在相对丰度改变。12周太极拳训练可通过影响放线菌门等菌群的相对丰度，以提高血清GLP-1水平，发挥降糖作用。影像学结果显示，T2DM患者的胰腺密度降低，胰腺体积减小。代谢组学结果表明T2DM存在多条糖、脂和氨基酸代谢通路的改变，其中太极拳可调节与GLP-1密切相关的支链氨基酸及色氨酸代谢通路。综上可知，太极拳可能通过调节肠道菌群及相关代谢通路，调节GLP-1的分泌，发挥治疗T2DM的作用。本项目研究结果为太极拳治疗优势病种的临床推广应用提供了科学依据，可促进中医养生康复功法的传承与发展。