Wang Linxi, Chen Zhou, Liu Xiaoying, Wang Lijing, Zhou Yu, Huang Jingze, Liu Zhiqing, Lin Donghai, Liu Libin
Department of Endocrinology and Metabolism, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou 350001, China.
Metabolites. 2023 Nov 1;13(11):1121. doi: 10.3390/metabo13111121.
High-sugar and high-fat diets cause significant harm to health, especially via metabolic diseases. In this study, the protective effects of the antidiabetic drug exenatide (synthetic exendin-4), a glucagon-like peptide 1 (GLP-1) receptor agonist, on high-fat and high-glucose (HFHG)-induced renal injuries were investigated in vivo and in vitro. In vivo and in vitro renal injury models were established. Metabolomic analysis based on H-nuclear magnetic resonance was performed to examine whether exenatide treatment exerts a protective effect against kidney injury in diabetic rats and to explore its potential molecular mechanism. In vivo, 8 weeks of exenatide treatment resulted in the regulation of most metabolites in the diabetes mellitus group. In vitro results showed that exendin-4 restored the mitochondrial functions of mesangial cells, which were perturbed by HFHG. The effects of exendin-4 included the improved antioxidant capacity of mesangial cells, increased the Bcl-2/Bax ratio, and reduced protein expression of cyt-c and caspase-3 activation. In addition, exendin-4 restored mesangial cell energy metabolism by increasing succinate dehydrogenase and phosphofructokinase activities and glucose consumption while inhibiting pyruvate dehydrogenase E1 activity. In conclusion, GLP-1 agonists improve renal injury in diabetic rats by ameliorating metabolic disorders. This mechanism could be partially related to mitochondrial functions and energy metabolism.
高糖和高脂饮食对健康造成重大危害，尤其是通过代谢性疾病。在本研究中，在体内和体外研究了抗糖尿病药物艾塞那肽（合成的艾塞那肽-4），一种胰高血糖素样肽1（GLP-1）受体激动剂，对高脂高糖（HFHG）诱导的肾损伤的保护作用。建立了体内和体外肾损伤模型。基于氢核磁共振的代谢组学分析用于检查艾塞那肽治疗是否对糖尿病大鼠的肾损伤发挥保护作用，并探索其潜在的分子机制。在体内，8周的艾塞那肽治疗导致糖尿病组中大多数代谢物的调节。体外结果表明，艾塞那肽-4恢复了被HFHG扰乱的系膜细胞的线粒体功能。艾塞那肽-4的作用包括提高系膜细胞的抗氧化能力，增加Bcl-2/Bax比值，并降低细胞色素c的蛋白表达和caspase-3的激活。此外，艾塞那肽-4通过增加琥珀酸脱氢酶和磷酸果糖激酶活性以及葡萄糖消耗，同时抑制丙酮酸脱氢酶E1活性，恢复了系膜细胞的能量代谢。总之，GLP-1激动剂通过改善代谢紊乱来改善糖尿病大鼠的肾损伤。该机制可能部分与线粒体功能和能量代谢有关。
