Synergistic effect of nano-selenium and metformin on type 2 diabetic rat model: Diabetic complications alleviation through insulin sensitivity, oxidative mediators and inflammatory markers
Synergistic effect of nano-selenium and metformin on type 2 diabetic rat model: Diabetic complications alleviation through insulin sensitivity, oxidative mediators and inflammatory markers
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DOI：
10.1371/journal.pone.0220779
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发表时间：
2019-08-23
期刊：
影响因子：
3.7
通讯作者：
Balbaa, Mahmoud
中科院分区：
文献类型：
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作者：
Abdulmalek, Shaymaa A.;Balbaa, Mahmoud
背景与目的本研究旨在探讨硒纳米颗粒（Se-NPs）治疗2型糖尿病（T2 DM）的新策略，观察Se-NPs单用及与标准降糖药二甲双胍（MET）联合应用对高脂饮食/链脲佐菌素（HFD/STZ）诱导的T2 DM的影响。随后单次低剂量注射35 mg/kg STZ以诱导T2 DM。在Se-NPs和MET给药8周后评价不同治疗策略对糖尿病并发症的协同作用。进行分子和生化分析，以找出我们的治疗对胰岛素敏感性，氧化介质和炎症markers.ResultsOur的观察结果表明，HFD/STZ诱导的大鼠血清和肝组织的毒性作用，导致诱导显着的氧化损伤和炎症与胰岛素信号通路的显着干扰。实验动物单独接受单药治疗-两剂Se-NP（0.1和0.4 mg/kg）和/或MET（100 mg/kg）以及联合治疗，均产生了显着的保护性抗糖尿病作用，表现为空腹血糖显着下降。8周治疗后的胰岛素水平。同时，活性胰岛素信号蛋白pIRS 1/pAKT/pGSK-3 β/pAMPK的表达水平明显提高。此外，硒纳米颗粒通过减轻细胞因子表达表现出抗炎作用，并恢复氧化应激和抗氧化状态之间的平衡。此外，抗糖尿病药物MET管理也表现出显着改善糖尿病并发症后的治疗period.ConclusionThis研究提供了强大的联合硒纳米粒子和MET作为一个有前途的治疗选择，协同治疗糖尿病并发症和胰岛素抵抗的作用机制。
Background and objectivesIn the present article, we explore a novel strategy of selenium nanoparticles (Se-NPs) for the treatment of type 2 diabetes mellitus (T2DM) by investigating the effect of Se-NPs alone and in combination with standard anti-diabetic drug metformin (MET) in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM.MethodsHFD was supplemented daily to experimental rats for 8 weeks, followed by a single low dose injection of 35 mg/kg of STZ to induce T2DM. The synergistic effect of the different therapeutic strategies on diabetic complications was evaluated after the Se-NPs and MET administration for 8 weeks. Molecular and biochemical analyses were conducted to figure out the effectiveness of our treatment on insulin sensitivity, oxidative mediators and inflammatory markers.ResultsOur observations demonstrated that HFD/STZ-induced rats have a toxic effect on serum and hepatic tissues resulted in inducing remarkable oxidative damage and hyper-inflammation with a significant disturbance in the insulin signaling pathway. Experimental animals either treated with mono-therapeutic-two doses Se-NPs (0.1 and 0.4 mg/kg) and/or MET (100 mg/kg) alone as well as the combined therapy resulted in a remarkable protective antidiabetic effect illustrated by significant decreases in fasting blood glucose and insulin levels after 8 weeks treatment. At the same time, the levels of active insulin signaling proteins pIRS1/pAKT/pGSK-3 beta/pAMPK were significantly improved. Moreover, Se-NPs exhibited an anti-inflammatory effect by the mitigation of cytokine expression and a balance between oxidative stress and antioxidant status was restored. Furthermore, the anti-diabetic drug MET administration also exhibited a significant improvement in diabetic complications after the treatment period.ConclusionThis study provides mightily the mechanism of action of combined Se-NPs and MET as a promising therapeutic alternative that synergistically alleviates most of diabetic complications and insulin resistance.