miR-765 targeting PDX1 impairs pancreatic β-cell function to induce type 2 diabetes.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2023-12-01 Epub Date: 2021-08-06 DOI:10.1080/13813455.2021.1946561

Li Zheng, Yalan Wang, Yanhong Li, Li Li, Xiaohong Wang, Yan Li

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引用次数: 4

Abstract

Type 2 diabetes (T2DM) is a chronic metabolism disorder with a symptom as pancreatic β-cell dysfunction. In this study, the bioinformatics analysis identified the key regulators (PDX1 and miR-765) in T2DM. By qRT-PCR and western blotting, miR-765 with high expression and PDX1 with low expression were observed in blood samples from T2DM patients and the T2DM cell model. Together with GSIS assay, CCK-8, TUNEL assay, glycolysis assay, and mitochondrial respiration assay, miR-765 overexpression impaired insulin secretion cell viability, glycolysis, and mitochondrial respiration, while enhanced cell apoptosis in pancreatic β-cell. The Luciferase reporter, RIP, and RNA pull-down assays showed that PDX1 was the target gene of miR-765 in pancreatic β-cell. Besides, the negative effect of miR-765 on pancreatic β-cell could be overturned by PDX1 overexpression. In conclusion, we confirmed that miR-765 could cause a detrimental effect on pancreatic β-cell survival and function by targeting PDX1, which might provide new insight for T2DM therapy.

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靶向PDX1的miR-765损害胰腺β细胞功能诱导2型糖尿病。

2型糖尿病(T2DM)是一种慢性代谢紊乱，其症状为胰腺β细胞功能障碍。在这项研究中，生物信息学分析确定了T2DM的关键调节因子(PDX1和miR-765)。通过qRT-PCR和western blotting，在T2DM患者和T2DM细胞模型的血液样本中观察到高表达的miR-765和低表达的PDX1。与GSIS实验、CCK-8、TUNEL实验、糖酵解实验和线粒体呼吸实验一起，miR-765过表达损害胰岛素分泌细胞活力、糖酵解和线粒体呼吸，同时增强胰腺β细胞的细胞凋亡。荧光素酶报告基因、RIP和RNA下拉实验表明，PDX1是胰腺β细胞中miR-765的靶基因。此外，miR-765对胰腺β细胞的负作用可以通过PDX1过表达而被推翻。总之，我们证实miR-765可能通过靶向PDX1对胰腺β细胞存活和功能产生不利影响，这可能为T2DM治疗提供新的见解。

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

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.