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积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能

OBJECTIVE: To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investig...

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Formato: Online Artículo Texto
Lenguaje:English
Publicado: 《浙江大学学报》编辑部 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409975/
https://www.ncbi.nlm.nih.gov/pubmed/37283103
http://dx.doi.org/10.3724/zdxbyxb-2022-0647
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collection PubMed
description OBJECTIVE: To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α. RESULTS: Asiatic acid with the dose of 25 mg·kg(-1)·d(-1) had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α. CONCLUSION: Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.
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spelling pubmed-104099752023-08-10 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能 Zhejiang Da Xue Xue Bao Yi Xue Ban Research Article OBJECTIVE: To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α. RESULTS: Asiatic acid with the dose of 25 mg·kg(-1)·d(-1) had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α. CONCLUSION: Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway. 《浙江大学学报》编辑部 2023-04-25 /pmc/articles/PMC10409975/ /pubmed/37283103 http://dx.doi.org/10.3724/zdxbyxb-2022-0647 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND 4.0 License (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Research Article
积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title_full 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title_fullStr 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title_full_unstemmed 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title_short 积雪草酸通过调控TNF-α/Mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
title_sort 积雪草酸通过调控tnf-α/mfn2通路改善2型糖尿病β细胞胰岛素分泌功能
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409975/
https://www.ncbi.nlm.nih.gov/pubmed/37283103
http://dx.doi.org/10.3724/zdxbyxb-2022-0647
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