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胰岛素载金和羧甲基壳聚糖纳米粒对 1 型糖尿病大鼠葡萄糖激酶和丙酮酸激酶基因表达的影响。

The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.

机构信息

Department of Quality Control, Hi Pharm Company for Manufacturing Pharmaceuticals and Chemicals, Cairo, Egypt.

Department of Biochemistry and Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt.

出版信息

J Food Biochem. 2022 Dec;46(12):e14447. doi: 10.1111/jfbc.14447. Epub 2022 Oct 11.

Abstract

The goal of this study was to see how effective subcutaneous (SC) insulin is and two different types of oral insulin-loaded nanoparticles (INS) including carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) separately and compare their effects on glucokinase, pyruvate kinase gene expressions, and other parameters in diabetes type one male Wistar rats. Seven groups of ten male Wistar rats for each group were formed at random including four control groups (n = 10) and three treatment groups (n = 10). The control groups consisted of four control groups (10 rats for each) and three treatment groups (10 rats for each). Normal control rats were not given any treatment, as were diabetic rats that were not given any treatment, and diabetic rats that were given oral nanoparticles (CMCNPs and AuNPs). Diabetic rats were given subcutaneous insulin, oral insulin-loaded carboxymethyl chitosan nanoparticles (INS-CMCNPs), and oral insulin-loaded gold nanoparticles (INS-AuNPs). The rats were treated for the final 3 weeks of the experiment, which lasted 4 weeks. CMCNPs and AuNPs presented a promising effect on pyruvate kinase and Glucokinase gene expressions compared to subcutaneous insulin. We also discovered that conjugating insulin to CMCNPs and AuNPs protects them from the insulin-degrading enzyme, which offers managed bioavailability. Furthermore, we investigated the effects of CMCNPs and AuNPs on several parameters and discovered that both have a significant effect in vivo, which enables glucose level regulation, and improves patient organ activity for better glucose consumption. PRACTICAL APPLICATIONS: In this paper, we discussed the effect of oral INS-CMCNPs and INS-AuNPs, and compared their effects on Glucokinase and pyruvate kinase gene expressions and other biochemical parameters in diabetes type one male Wistar rats. On the other hand, we investigated the impact of oral INS and subcutaneous insulin separately on the same parameters and their effect on the histology of the liver and pancreas of diabetic rats. According to our research, as we discussed the different mechanisms of INS-CMCNPs and INS-AuNPs, they presented a promising effect compared to SC insulin. They can be used to keep oral insulin safe from the environment of the gastrointestinal system to overcome all the barriers, improve the therapeutic, and clinical outcomes of insulin by maintaining its desired concentration inside the body, ending the panic of the patient from receiving insulin by the SC injection by increasing his satisfaction with receiving accurate oral insulin doses.

摘要

本研究的目的是观察皮下(SC)胰岛素的有效性,以及两种不同类型的口服胰岛素负载纳米颗粒(INS),包括羧甲基壳聚糖纳米颗粒(CMCNPs)和金纳米颗粒(AuNPs),分别比较它们对葡萄糖激酶、丙酮酸激酶基因表达和其他参数的影响在一型糖尿病雄性 Wistar 大鼠中。随机形成了七组十只雄性 Wistar 大鼠,每组包括四个对照组(n=10)和三个治疗组(n=10)。对照组包括四个对照组(每组 10 只)和三个治疗组(每组 10 只)。正常对照组大鼠未给予任何治疗,糖尿病未给予任何治疗的大鼠也未给予任何治疗,糖尿病大鼠给予口服纳米颗粒(CMCNPs 和 AuNPs)。糖尿病大鼠给予皮下胰岛素、口服胰岛素负载羧甲基壳聚糖纳米颗粒(INS-CMCNPs)和口服胰岛素负载金纳米颗粒(INS-AuNPs)。实验的最后 3 周,即为期 4 周的时间里,大鼠接受了治疗。与皮下胰岛素相比,CMCNPs 和 AuNPs 对丙酮酸激酶和葡萄糖激酶基因表达表现出有希望的效果。我们还发现,将胰岛素与 CMCNPs 和 AuNPs 缀合可以保护它们免受胰岛素降解酶的影响,从而提供可管理的生物利用度。此外,我们研究了 CMCNPs 和 AuNPs 对几个参数的影响,发现它们在体内都有显著的效果,能够调节血糖水平,改善患者器官活性,促进更好的葡萄糖消耗。实际应用:在本文中,我们讨论了口服 INS-CMCNPs 和 INS-AuNPs 的效果,并比较了它们对一型糖尿病雄性 Wistar 大鼠葡萄糖激酶和丙酮酸激酶基因表达及其他生化参数的影响。另一方面,我们分别研究了口服 INS 和皮下胰岛素对同一参数的影响及其对糖尿病大鼠肝脏和胰腺组织学的影响。根据我们的研究,正如我们讨论的 INS-CMCNPs 和 INS-AuNPs 的不同机制一样,它们与 SC 胰岛素相比表现出有希望的效果。它们可用于将口服胰岛素安全地隔离在胃肠道环境之外,克服所有障碍,通过维持体内所需的浓度来提高胰岛素的治疗和临床效果,通过增加患者对准确口服胰岛素剂量的满意度,消除患者对 SC 注射的恐惧。

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