Circular RNA PIP5K1A Promotes Glucose and Lipid Metabolism Disorders and Inflammation in Type 2 Diabetes Mellitus.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biotechnology Pub Date : 2024-12-01 Epub Date: 2023-11-15 DOI:10.1007/s12033-023-00954-1
Ge Song, YiQian Zhang, YiHua Jiang, Huan Zhang, Wen Gu, Xiu Xu, Jing Yao, ZhengFang Chen
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Abstract

Disorders of glucose and lipid metabolism are an important cause of type 2 diabetes mellitus (T2DM). Identifying the molecular mechanism of metabolic disorders is key to the treatment of T2DM. The study was to investigate the effect of circRNA PIP5K1A (circPIP5K1A) on glucose and lipid metabolism and inflammation in T2DM rats. A T2DM rat model was established, and then the T2DM rats were injected with lentiviral vectors that interfere with circPIP5K1A, miR-552-3p, or ENO1 expression. Fasting blood glucose (FBG) and fasting insulin (FINS) levels of rats were detected by an automatic analyzer and insulin detection kit, and HOMA-IR was calculated. Lipid metabolism was assessed by measuring serum levels of TG, TC, LDL-C, leptin, and resistin. Serum levels of inflammatory factors (TNF-α and IL-6) were detected by ELISA. The pathological conditions of pancreatic tissue were observed by HE staining. circPIP5K1A, miR-552-3p and ENO1 levels were recorded. The experimental results showed that circPIP5K1A and ENO1 were up-regulated, and miR-552-3p was down-regulated in T2DM rats. Down-regulating circPIP5K1A or up-regulating miR-552-3p reduced blood glucose and lipid levels, inhibited inflammation, and improved pancreatic histopathological changes in T2DM rats. In addition, up-regulating ENO1 rescued the ameliorating effects of down-regulated circPIP5K1A on T2DM rats. In general, downregulating circPIP5K1A improves insulin resistance and lipid metabolism disorders and inhibits inflammation by targeting miR-552-3p to mediate ENO1 expression.

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环状RNA PIP5K1A促进2型糖尿病糖脂代谢紊乱和炎症
糖脂代谢紊乱是2型糖尿病(T2DM)的重要病因。明确代谢紊乱的分子机制是治疗T2DM的关键。本研究旨在探讨circRNA PIP5K1A (circPIP5K1A)对T2DM大鼠糖脂代谢及炎症的影响。建立T2DM大鼠模型,然后给T2DM大鼠注射干扰circPIP5K1A、miR-552-3p或ENO1表达的慢病毒载体。采用全自动血糖仪和胰岛素检测试剂盒检测大鼠空腹血糖(FBG)和空腹胰岛素(FINS)水平,并计算HOMA-IR。脂质代谢通过测定血清TG、TC、LDL-C、瘦素和抵抗素水平来评估。ELISA法检测血清炎症因子(TNF-α、IL-6)水平。HE染色观察胰腺组织病理情况。记录circPIP5K1A、miR-552-3p和ENO1水平。实验结果显示,T2DM大鼠circPIP5K1A和ENO1上调,miR-552-3p下调。下调cirpip5k1a或上调miR-552-3p可降低T2DM大鼠的血糖和血脂水平,抑制炎症,改善胰腺组织病理学改变。此外,上调ENO1可恢复下调cirpip5k1a对T2DM大鼠的改善作用。一般来说,下调cirpip5k1a可通过靶向miR-552-3p介导ENO1表达,改善胰岛素抵抗和脂质代谢紊乱,抑制炎症。
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来源期刊
Molecular Biotechnology
Molecular Biotechnology 医学-生化与分子生物学
CiteScore
4.10
自引率
3.80%
发文量
165
审稿时长
6 months
期刊介绍: Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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