Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
PLoS One. 2019 Aug 23;14(8):e0220779. doi: 10.1371/journal.pone.0220779. eCollection 2019.
In 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.
HFD 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.
Our 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 anti-diabetic 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-3β/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.
This 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.
在本文中，我们探讨了一种新型的硒纳米粒子（Se-NPs）治疗 2 型糖尿病（T2DM）的策略，研究了 Se-NPs 单独使用以及与标准抗糖尿病药物二甲双胍（MET）联合使用对高脂肪饮食/链脲佐菌素（HFD/STZ）诱导的 T2DM 的影响。
实验大鼠每天补充 HFD8 周，然后单次低剂量注射 35mg/kg 的 STZ 诱导 T2DM。在 Se-NPs 和 MET 给药 8 周后，评估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，以确定我们的治疗方法对胰岛素敏感性、氧化介质和炎症标志物的有效性。
我们的观察结果表明，HFD/STZ 诱导的大鼠对血清和肝组织具有毒性作用，导致显著的氧化损伤和过度炎症，同时胰岛素信号通路也受到显著干扰。实验动物单独接受两种剂量的 Se-NPs（0.1 和 0.4mg/kg）和/或 MET（100mg/kg）的单一治疗，以及联合治疗，均表现出显著的保护抗糖尿病作用，表现为 8 周治疗后空腹血糖和胰岛素水平显著降低。同时，活性胰岛素信号蛋白 pIRS1/pAKT/pGSK-3β/pAMPK 的水平显著改善。此外，Se-NPs 通过减轻细胞因子表达发挥抗炎作用，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 的给药在治疗期间也显著改善了糖尿病并发症。
本研究提供了 Se-NPs 和 MET 联合作为一种有前途的治疗选择的作用机制，可协同缓解大多数糖尿病并发症和胰岛素抵抗。
