基于胰腺代谢组学研究有氧运动干预大鼠胰岛素抵抗的作用机制
Mechanism of Aerobic Exercise Intervention on Insulin Resistance in Rats Based on Pancreatic Metabonomics

摘要：目的：应用核磁共振(1H-NMR)代谢组学方法研究有氧运动干预胰岛素抵抗（Insulin resistance, IR）的作用机制。方法：2月龄大鼠40只，随机分为正常饮食组和高脂饮食组喂养5周建模，采用高胰岛素-正葡萄糖改良钳夹术对大鼠IR进行评价，随之将其分为对照组(N)、模型组(IR)和模型运动组(IRe)。IRe组有氧运动干预6周，之后所有大鼠采用钳夹术评估IR，ELISA检测血清FINS，1H-NMR测定大鼠胰腺组织代谢物，多元统计分析代谢物谱差异，MetaboAnalyst分析代谢通路，受试者工作曲线（ROC）筛选潜在生物标志物。结果：1） 与N组相比，IR组FINS显著提高，GIR显著下降；与IR组相比，IRe组大鼠体重、FINS均显著下降，GIR显著性提高。2）与N组相比，IR组胰腺组织中11个代谢物存在差异，分别与6条代谢通路密切相关，ROC分析发现5个IR大鼠胰腺生物标志物。3）IRe组相对于IR组，柠檬酸、谷氨酸、谷氨酰胺等5个生物标志物不同程度回调。结论：6周有氧运动可以显著改善高脂饮食诱导的大鼠IR状态，其机制可能与有氧运动能够不同程度回调IR大鼠胰腺生物标志物，改善其涉及的代谢通路有关。
Aastract: Objective: To study the mechanism of aerobic exercise intervention on insulin resistance (IR) by 1H-NMR metabolomics. Methods: Forty 2-month-old rats were randomly divided into normal diet group and high-fat diet group for 5 weeks. IR Rats were evaluated by hyperinsulinemic-glucose improved clamp and then divided into control group (N ), model group (IR) and model exercise group (IRe). The rats of IRe group finished 6 weeks aerobic. After the experiment, IR of all rats were examined by clamp, serum FINS was tested by FINS, pancreatic tissue metabolites were explored by 1H-NMR and analyzed by multivariate statistical analysis, metabolic pathways were detecteb by MetaboAnalyst, and potential biomarkers were screened by the ROC. Results: 1) Compared with N group, FINS in IR group increased significantly and GIR decreased significantly. Compared with IR group, the body weight and FINS of IRe group decreased significantly and GIR increased significantly. 2) Compared with N group, 11 metabolites in the pancreas tissue of the IR group were different and were closely related to the six metabolic pathways, and 5 IR pancreatic biomarkers were found by ROC analysis. 3) Compared with IR group, 5 biomarkers, such as citric acid, glutamic acid and glutamine, were changed to different degrees in IRe group. Conclusions: This 6-week aerobic exercise can significantly improve the IR induced by high-fat diet, and its mechanism may be related the fact that aerobic exercise can alter the pancreatic biomarkers in different degrees in IR rats and then improve their metabolic pathways