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通过IR/GLUT4介导的信号机制降低高脂饮食和链脲佐菌素诱导的2型糖尿病大鼠的肌肉胰岛素抵抗

Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats.

作者信息

Roy Jeane Rebecca, Janaki Coimbatore Sadagopan, Jayaraman Selvaraj, Periyasamy Vijayalakshmi, Balaji Thotakura, Vijayamalathi Madhavan, Veeraraghavan Vishnu Priya

机构信息

Department of Anatomy, Bhaarath Medical College and Hospital, Bharath Institute of Higher Education and Research (BIHER), Chennai 600 073, Tamil Nadu, India.

Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600 077, Tamil Nadu, India.

出版信息

Antioxidants (Basel). 2022 Oct 21;11(10):2081. doi: 10.3390/antiox11102081.

Abstract

In the management of type 2 diabetes, oral antidiabetic drugs have several side effects, which in turn have led the pharmaceutical industry to search for good therapeutic, non-toxic and reliable drugs. is one of several plants in nature that have been found to possess anti-diabetic properties. Despite studies being focused on the antidiabetic activity of , the molecular mechanism against high fat diet induced insulin resistance is yet to be identified. The role of was evaluated on insulin signaling molecules, such as the insulin receptor (IR) and glucose transporter-4 (GLUT4) in high fat, diet-streptozotocin induced type 2 diabetic rats, and analyzed the bioactive compounds of against IR and GLUT4 via molecular docking and dynamics. The ethanolic extract of leaves (600 mg/kg of body weight) was given daily to male wistar rats for 45 days and we observed the various biochemical parameters, gene expression analysis and histopathology of skeletal muscle. Molecular docking and dynamics were undertaken to understand the bioactive compounds with the greatest hit rate. treatment was able to control blood glucose levels, the lipid profile and serum insulin, but it facilitated tissue antioxidant enzymes and IR and GLUT4 levels. The in-silico study showed that kaempferol, quercitin and transferulic acid were the top three ligands with the greatest hit rate against the protein targets. Our preliminary findings, for the first time, showed that reinstates the glycemic effect in the diabetic skeletal muscle by accelerating the expression of IR and GLUT4.

摘要

在2型糖尿病的管理中,口服抗糖尿病药物有几种副作用,这反过来促使制药行业寻找疗效好、无毒且可靠的药物。[植物名称]是自然界中已被发现具有抗糖尿病特性的几种植物之一。尽管研究集中在[植物名称]的抗糖尿病活性上,但针对高脂饮食诱导的胰岛素抵抗的分子机制尚未确定。在高脂饮食-链脲佐菌素诱导的2型糖尿病大鼠中,评估了[植物名称]对胰岛素信号分子,如胰岛素受体(IR)和葡萄糖转运蛋白4(GLUT4)的作用,并通过分子对接和动力学分析了[植物名称]针对IR和GLUT4的生物活性化合物。每天给雄性Wistar大鼠灌胃[植物名称]叶乙醇提取物(600毫克/千克体重),持续45天,我们观察了各种生化参数、基因表达分析和骨骼肌组织病理学。进行分子对接和动力学研究以了解命中率最高的生物活性化合物。[植物名称]治疗能够控制血糖水平、血脂谱和血清胰岛素水平,但它促进了组织抗氧化酶以及IR和GLUT4水平。计算机模拟研究表明,山奈酚、槲皮素和阿魏酸是针对蛋白质靶点命中率最高的前三种配体。我们的初步研究结果首次表明,[植物名称]通过加速IR和GLUT4的表达恢复糖尿病骨骼肌中的血糖效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9762/9598374/693baae2a545/antioxidants-11-02081-g001.jpg

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