Sildenafil Enhances the Therapeutic Effect of Islet Transplantation for Diabetic Peripheral Neuropathy via mTOR/S6K1 Pathway.

IF 2.3 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

International Journal of Endocrinology Pub Date : 2023-10-07 eCollection Date: 2023-01-01 DOI:10.1155/2023/8199029

Xiandong Zhu, Shangjing Xie, Jiawei Chen, Qiaohong Lu, Xiaowu Wang, Feixiang Duan, Sinian Xu, Yan Zhang, Hongjian Huang, Yongqiang Wang, Hongwei Wang, Bicheng Chen, Huanjie Huang

{"title":"Sildenafil Enhances the Therapeutic Effect of Islet Transplantation for Diabetic Peripheral Neuropathy via mTOR/S6K1 Pathway.","authors":"Xiandong Zhu, Shangjing Xie, Jiawei Chen, Qiaohong Lu, Xiaowu Wang, Feixiang Duan, Sinian Xu, Yan Zhang, Hongjian Huang, Yongqiang Wang, Hongwei Wang, Bicheng Chen, Huanjie Huang","doi":"10.1155/2023/8199029","DOIUrl":null,"url":null,"abstract":"Purpose: This study aimed to investigate the potential mechanism underlying the therapeutic effect of sildenafil in combination with islet transplantation for diabetic peripheral neuropathy.Methods: A streptozotocin-induced diabetic mouse model was established to evaluate the effects of islet transplantation and sildenafil intervention. The mice were subjected to different interventions for 6 weeks, and histopathological staining and immunohistochemistry techniques were employed to examine the pathological changes and protein expressions of BDNF, MBP, and cleaved caspase-3 in the sciatic nerve tissue. Moreover, RSC96 cells were cocultured with islet cells and sildenafil under high glucose conditions to investigate the potential involvement of the mTOR/S6K1 pathway, BDNF, and MBP proteins. Western blotting was used to detect protein expression in each group.Results: The results showed that islet transplantation can restore sciatic nerve injury in diabetic mice, and sildenafil can enhance the therapeutic effect of islet transplantation. In addition, the combination of sildenafil and islet cells significantly upregulated the expression levels of mTOR/S6K1, BDNF, and MBP in RSC96 cells under high glucose conditions.Conclusions: Islet transplantation can reverse sciatic nerve injury in diabetic mice, and islet cells exhibit a protective effect on RSC96 cells under high glucose conditions via the activation of the mTOR/S6K1 pathway. Sildenafil enhances the therapeutic effect of islet transplantation, which may represent a potential treatment strategy for diabetic peripheral neuropathy.","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576648/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2023/8199029","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: This study aimed to investigate the potential mechanism underlying the therapeutic effect of sildenafil in combination with islet transplantation for diabetic peripheral neuropathy.

Methods: A streptozotocin-induced diabetic mouse model was established to evaluate the effects of islet transplantation and sildenafil intervention. The mice were subjected to different interventions for 6 weeks, and histopathological staining and immunohistochemistry techniques were employed to examine the pathological changes and protein expressions of BDNF, MBP, and cleaved caspase-3 in the sciatic nerve tissue. Moreover, RSC96 cells were cocultured with islet cells and sildenafil under high glucose conditions to investigate the potential involvement of the mTOR/S6K1 pathway, BDNF, and MBP proteins. Western blotting was used to detect protein expression in each group.

Results: The results showed that islet transplantation can restore sciatic nerve injury in diabetic mice, and sildenafil can enhance the therapeutic effect of islet transplantation. In addition, the combination of sildenafil and islet cells significantly upregulated the expression levels of mTOR/S6K1, BDNF, and MBP in RSC96 cells under high glucose conditions.

Conclusions: Islet transplantation can reverse sciatic nerve injury in diabetic mice, and islet cells exhibit a protective effect on RSC96 cells under high glucose conditions via the activation of the mTOR/S6K1 pathway. Sildenafil enhances the therapeutic effect of islet transplantation, which may represent a potential treatment strategy for diabetic peripheral neuropathy.

Abstract Image

查看原文本刊更多论文

西地那非通过mTOR/S6K1途径增强胰岛移植治疗糖尿病周围神经病变的疗效。

目的：本研究旨在探讨西地那非联合胰岛移植治疗糖尿病周围神经病变的潜在机制。方法：建立链脲佐菌素诱导的糖尿病小鼠模型，评价胰岛移植和西地那非干预的效果。对小鼠进行不同的干预6 周，采用组织病理学染色和免疫组织化学技术检测坐骨神经组织中BDNF、MBP和裂解的胱天蛋白酶-3的病理变化和蛋白表达。此外，在高糖条件下，将RSC96细胞与胰岛细胞和西地那非共培养，以研究mTOR/S6K1途径、BDNF和MBP蛋白的潜在参与。用蛋白质印迹法检测各组的蛋白质表达。结果：胰岛移植可恢复糖尿病小鼠坐骨神经损伤，西地那非可提高胰岛移植的治疗效果。此外，西地那非和胰岛细胞的组合在高糖条件下显著上调RSC96细胞中mTOR/S6K1、BDNF和MBP的表达水平。结论：胰岛移植可逆转糖尿病小鼠坐骨神经损伤，胰岛细胞在高糖条件下通过激活mTOR/S6K1通路对RSC96细胞具有保护作用。西地那非增强了胰岛移植的治疗效果，这可能是糖尿病周围神经病变的一种潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

International Journal of Endocrinology ENDOCRINOLOGY & METABOLISM-

CiteScore

5.20

自引率

0.00%

发文量

147

审稿时长

1 months

期刊介绍： International Journal of Endocrinology is a peer-reviewed, Open Access journal that provides a forum for scientists and clinicians working in basic and translational research. The journal publishes original research articles, review articles, and clinical studies that provide insights into the endocrine system and its associated diseases at a genomic, molecular, biochemical and cellular level.