The role of glucose transporters (GLUTs) in diabetes mellitus has become more prominent as a possible therapeutic target. In the present study, we aimed to compare the effect of zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), and docosahexaenoic acid (DHA) alone or loaded in ZnONPs or AgNPs on insulin signaling pathway and GLUTs expression in diabetic rats. In the experimental part, rats were divided into seven groups; control, diabetic, and the other five groups were diabetic received different treatments. Fasting blood sugar (FBS), serum level of insulin, insulin resistance (IR), and serum level of phosphatidylinositol 3-kinase (PI3K) were evaluated. In addition, insulin expression in pancreatic islets was assessed by immunohistochemical analysis, and the expression of liver GLUTs 1, 2, and 4 and liver insulin receptor substrate-1 (IRS-1) was evaluated by real-time polymerase chain reactions (RT-PCR).

The results of the current study showed that ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs attenuated levels of FBS, insulin and decreased IR in diabetic rats through enhancing the expression of GLUTs as well as IRS-1 and PI3K. Furthermore, AgNPs loaded with DHA showed the most significance with high comparability to the control group.

In conclusion, this study elucidated the role of GLUTs and IRS-1 in diabetes and introduced novel characteristics of ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs as a therapeutic modality to activate GLUTs and IRS1, which may be beneficial for diabetic patients with IR.

葡萄糖转运蛋白（GLUT）作为可能的治疗靶点在糖尿病中的作用变得更加突出。在本研究中，我们的目的是比较氧化锌纳米颗粒（ZnONPs）、纳米银（AgNPs）和二十二碳六烯酸（DHA）单独或负载在ZnONPs或AgNPs中对糖尿病大鼠胰岛素信号通路和GLUTs表达的影响。实验部分，将大鼠分为七组；对照组、糖尿病组和其他五组糖尿病患者接受了不同的治疗。评估空腹血糖（FBS）、血清胰岛素水平、胰岛素抵抗（IR）和血清磷脂酰肌醇3激酶（PI3K）水平。此外，通过免疫组织化学分析评估胰岛中的胰岛素表达，并通过实时聚合酶链反应（RT- PCR）。

目前的研究结果表明，单独的 ZnONPs、AgNPs 和 DHA 或负载在 ZnONPs 或 AgNPs 中可以通过增强 GLUT 以及 IRS-1 和 PI3K 的表达来降低糖尿病大鼠的 FBS、胰岛素水平并降低 IR。此外，负载 DHA 的 AgNPs 表现出最显着的效果，与对照组具有很高的可比性。

总之，本研究阐明了 GLUTs 和 IRS-1 在糖尿病中的作用，并介绍了单独的 ZnONPs、AgNPs 和 DHA 或负载 ZnONPs 或 AgNPs 的新特性，作为激活 GLUTs 和 IRS1 的治疗方式，这可能有益于糖尿病IR 患者。