匙羹藤酸通过调节 Pdx1 表达改善胰腺β细胞功能障碍：β细胞再生的一种可能策略。

Gymnemic Acid Ameliorates Pancreatic β-Cell Dysfunction by Modulating Pdx1 Expression: A Possible Strategy for β-Cell Regeneration.

机构信息

Department of Medical Biochemistry, Dr ALM PG IBMS, University of Madras, Taramani Campus, Taramani, Chennai, 600 113, India.

Department of Pathology, Dr ALM PG IBMS, University of Madras, Taramani Campus, Taramani, Chennai, India.

出版信息

Tissue Eng Regen Med. 2022 Jun;19(3):603-616. doi: 10.1007/s13770-022-00435-7. Epub 2022 Feb 25.

DOI:10.1007/s13770-022-00435-7

PMID:35212973

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9130387/

Abstract

BACKGROUND

Endogenous pancreatic β-cell regeneration is a promising therapeutic approach for enhancing β-cell function and neogenesis in diabetes. Various findings have reported that regeneration might occur via stimulating β-cell proliferation, neogenesis, or conversion from other pancreatic cells to β-like cells. Although the current scenario illustrates numerous therapeutic strategies and approaches that concern endogenous β-cell regeneration, all of them have not been successful to a greater extent because of cost effectiveness, availability of suitable donors and rejection in case of transplantation, or lack of scientific evidence for many phytochemicals derived from plants that have been employed in traditional medicine. Therefore, the present study aims to investigate the effect of gymnemic acid (GA) on β-cell regeneration in streptozotocin-induced type 1 diabetic rats and high glucose exposed RIN5-F cells.

METHODS

The study involves histopathological and immunohistochemical analysis to examine the islet's architecture. Quantitative polymerase chain reaction (qPCR) and/or immunoblot were employed to quantify the β-cell regeneration markers and cell cycle proliferative markers.

RESULTS

The immunoexpression of E-cadherin, β-catenin, and phosphoinositide 3-kinases/protein kinase B were significantly increased in GA-treated diabetic rats. On the other hand, treatment with GA upregulated the pancreatic regenerative transcription factor viz. pancreatic duodenal homeobox 1, Neurogenin 3, MafA, NeuroD1, and β-cells proliferative markers such as CDK4, and Cyclin D1, with a simultaneous downregulation of the forkhead box O, glycogen synthase kinase-3, and p21 in diabetic treated rats. Adding to this, we noticed increased nuclear localization of Pdx1 in GA treated high glucose exposed RIN5-F cells.

CONCLUSION

Our results suggested that GA acts as a potential therapeutic candidate for endogenous β-cell regeneration in treating type 1 diabetes.

摘要

背景

内源性胰腺 β 细胞再生是增强糖尿病患者 β 细胞功能和新生的有前途的治疗方法。各种研究结果表明，再生可能通过刺激 β 细胞增殖、新生或从其他胰腺细胞转化为 β 样细胞来实现。尽管目前的情况表明存在许多与内源性 β 细胞再生相关的治疗策略和方法，但由于成本效益、合适供体的可用性以及移植时的排斥反应，或者许多来自植物的植物化学物质缺乏科学证据，这些方法在很大程度上都没有成功，这些植物化学物质已用于传统医学。因此，本研究旨在研究瓜纳酸（GA）对链脲佐菌素诱导的 1 型糖尿病大鼠和高葡萄糖暴露的 RIN5-F 细胞中 β 细胞再生的影响。

方法

该研究包括组织病理学和免疫组织化学分析，以检查胰岛的结构。采用定量聚合酶链反应（qPCR）和/或免疫印迹法来定量 β 细胞再生标志物和细胞周期增殖标志物。

结果

GA 处理的糖尿病大鼠中 E-钙粘蛋白、β-连环蛋白和磷酸肌醇 3-激酶/蛋白激酶 B 的免疫表达明显增加。另一方面，GA 处理上调了胰腺再生转录因子，即胰腺十二指肠同源盒 1、神经基因 3、MAF 转录因子 A、NeuroD1 和β 细胞增殖标志物，如 CDK4 和细胞周期蛋白 D1，同时下调叉头框 O、糖原合成酶激酶 3 和 p21 在糖尿病治疗大鼠中。此外，我们注意到在 GA 处理的高葡萄糖暴露的 RIN5-F 细胞中，Pdx1 的核定位增加。