Plantamajoside improves type 2 diabetes mellitus pancreatic β-cell damage by inhibiting endoplasmic reticulum stress through Dnajc1 up-regulation.

IF 4.2 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2025-02-15 DOI:10.4239/wjd.v16.i2.99053

Duo Wang, Yuan-Song Wang, Hong-Min Zhao, Peng Lu, Meng Li, Wei Li, Huan-Tian Cui, Zhong-Yong Zhang, Shu-Quan Lv

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引用次数: 0

Abstract

Background: Plantamajoside (PMS) has shown potential in mitigating cell damage caused by high glucose (HG) levels. Despite this, the precise therapeutic effects of PMS on type 2 diabetes mellitus (T2DM) and the underlying regulatory mechanisms require further exploration.

Aim: To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.

Methods: An in vitro damage model of MIN6 cells was established using HG and palmitic acid (PA). PMS's protective effect on cell damage was assessed. Next, transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells. Furthermore, the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated. A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.

Results: PMS intervention ameliorated cell injury in HG + PA-induced MIN6 cell damage. Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS, with significant downregulation of the gene Dnajc1. Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors (Bax, CytC) and endoplasmic reticulum stress (ERS)-related factors [ATF6, XBP1, Ddit3 (CHOP), GRP78], while promoting the expression of Bcl-2 and Dnajc1. Additionally, the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing. Furthermore, in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage, suppressed the expression of apoptosis-related factors (Bax, CytC), and ERS-related factors [ATF6, XBP1, Ddit3 (CHOP), GRP78], while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.

Conclusion: PMS intervention could alleviate pancreatic tissue damage effectively. The mechanism of action involves Dnajc1 activation, which subsequently inhibits apoptosis and ERS, ameliorating damage to pancreatic β-cells.

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车前草皂苷通过上调Dnajc1抑制内质网应激，改善2型糖尿病胰腺β细胞损伤。

背景：车前草皂苷（PMS）已显示出减轻高葡萄糖（HG）水平引起的细胞损伤的潜力。尽管如此，经前症候群对2型糖尿病（T2DM）的确切治疗作用及其调控机制仍需进一步探索。目的：通过体内和体外实验，探讨经前多糖对小鼠2型糖尿病的治疗作用，并阐明其作用机制。方法：用HG和棕榈酸（PA）建立MIN6细胞体外损伤模型。观察PMS对细胞损伤的保护作用。接下来，转录组学研究了PMS治疗如何影响MIN6细胞的基因表达。进一步证实了PMS对内质网蛋白加工和细胞凋亡通路的影响。采用T2DM小鼠模型验证PMS在体内的治疗作用及机制。结果：PMS干预可改善HG + pa诱导的MIN6细胞损伤。转录组学分析显示，经PMS处理的细胞内质网和凋亡通路的蛋白质加工丰富，Dnajc1基因显著下调。进一步验证表明，PMS显著抑制凋亡相关因子（Bax、CytC）和内质网应激（ERS）相关因子[ATF6、XBP1、Ddit3 （CHOP）、GRP78]的表达，同时促进Bcl-2、Dnajc1的表达。此外，PMS对ERS和凋亡的抑制作用在Dnajc1沉默后被消除。此外，体内实验表明，PMS干预可有效改善T2DM模型小鼠胰腺损伤，抑制凋亡相关因子（Bax、CytC）和ers相关因子[ATF6、XBP1、Ddit3 （CHOP）、GRP78]的表达，同时促进Bcl-2和Dnajc1的表达。结论：经前综合症干预可有效减轻胰腺组织损伤。其作用机制包括激活Dnajc1，随后抑制细胞凋亡和ERS，改善对胰腺β细胞的损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.