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大蒜素通过AMPK/mTOR介导的自噬途径对1型糖尿病的保护作用。

The protective roles of allicin on type 1 diabetes mellitus through AMPK/mTOR mediated autophagy pathway.

作者信息

Qian Rengcheng, Chen Huihui, Lin Hongzhou, Jiang Yalan, He Pingping, Ding Yinjuan, Wu Huilan, Peng Yongmiao, Wang Lingfei, Chen Congde, Wang Dexuan, Ji Weiping, Guo Xiaoling, Shan Xiaoou

机构信息

Department of Pediatrics, The Second Schoozl of Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Key Laboratory of Children Genitourinary Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Front Pharmacol. 2023 Feb 3;14:1108730. doi: 10.3389/fphar.2023.1108730. eCollection 2023.


DOI:10.3389/fphar.2023.1108730
PMID:36817124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9937553/
Abstract

Type 1 diabetes mellitus (T1DM) is one of the most common endocrine and metabolic diseases in children. Pancreatic β cells are thought to be critical cells involved in the progression of T1DM, and their injury would directly lead to impaired insulin secretion. To investigate the protective effects of allicin on pancreatic β cell injury and elucidate the underlying mechanism. The streptozotocin (STZ)-induced mouse T1DM model and STZ-induced pancreatic β cell Min6 model in vitro were used to explore the effects of allicin on T1DM. The experiments include fasting blood glucose test, oral glucose tolerance detection, HE staining, immunohistochemistry, immunofluorescence, TUNEL staining, western blot, real-time quantitative PCR (RT-qPCR), and flow cytometry. Allicin could significantly decrease blood glucose level, improve islet structure and insulin expression, and inhibit apoptosis to reduce STZ-induced pancreatic β cell injury and loss through activating AMPK/mTOR mediated autophagy pathway. Allicin treatment significantly reduced STZ-induced T1DM progression, suggesting that allicin may be a potential therapy option for T1DM patients.

摘要

1型糖尿病(T1DM)是儿童中最常见的内分泌和代谢疾病之一。胰腺β细胞被认为是参与T1DM进展的关键细胞,其损伤会直接导致胰岛素分泌受损。为了研究大蒜素对胰腺β细胞损伤的保护作用并阐明其潜在机制。采用链脲佐菌素(STZ)诱导的小鼠T1DM模型和体外STZ诱导的胰腺β细胞Min6模型来探究大蒜素对T1DM的影响。实验包括空腹血糖测试、口服葡萄糖耐量检测、苏木精-伊红(HE)染色、免疫组织化学、免疫荧光、末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)染色、蛋白质免疫印迹法(western blot)、实时定量聚合酶链反应(RT-qPCR)和流式细胞术。大蒜素可通过激活AMPK/mTOR介导的自噬途径,显著降低血糖水平,改善胰岛结构和胰岛素表达,并抑制细胞凋亡,以减轻STZ诱导的胰腺β细胞损伤和丢失。大蒜素治疗显著减轻了STZ诱导的T1DM进展,表明大蒜素可能是T1DM患者的一种潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/4cfdaa5b66a2/fphar-14-1108730-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/cea748b88b51/fphar-14-1108730-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/2f0359c6ad37/fphar-14-1108730-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/f3893ae749b7/fphar-14-1108730-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/7add0ffdc62b/fphar-14-1108730-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/d34855a28ebc/fphar-14-1108730-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/aa91c58165e1/fphar-14-1108730-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/92380a4fa399/fphar-14-1108730-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/4cfdaa5b66a2/fphar-14-1108730-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/cea748b88b51/fphar-14-1108730-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/2f0359c6ad37/fphar-14-1108730-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/f3893ae749b7/fphar-14-1108730-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/7add0ffdc62b/fphar-14-1108730-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/d34855a28ebc/fphar-14-1108730-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/aa91c58165e1/fphar-14-1108730-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/92380a4fa399/fphar-14-1108730-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdd/9937553/4cfdaa5b66a2/fphar-14-1108730-g008.jpg

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引用本文的文献

[1]
A novel microRNA promotes coxsackievirus B4 infection of pancreatic β cells.

Front Immunol. 2024-12-4

[2]
Targeting Autophagy: A Promising Therapeutic Strategy for Diabetes Mellitus and Diabetic Nephropathy.

Diabetes Ther. 2024-10

本文引用的文献

[1]
cPKCγ Deficiency Exacerbates Autophagy Impairment and Hyperphosphorylated Tau Buildup through the AMPK/mTOR Pathway in Mice with Type 1 Diabetes Mellitus.

Neurosci Bull. 2022-10

[2]
Anti-Inflammatory and Pro-Autophagy Effects of the Cannabinoid Receptor CB2R: Possibility of Modulation in Type 1 Diabetes.

Front Pharmacol. 2022-1-18

[3]
Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation.

NPJ Biofilms Microbiomes. 2022-1-27

[4]
Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment.

Antioxidants (Basel). 2021-12-30

[5]
Resveratrol mitigates pancreatic TF activation and autophagy-mediated beta cell death via inhibition of CXCL16/ox-LDL pathway: A novel protective mechanism against type 1 diabetes mellitus in mice.

Eur J Pharmacol. 2021-6-15

[6]
Allicin Attenuated Advanced Oxidation Protein Product-Induced Oxidative Stress and Mitochondrial Apoptosis in Human Nucleus Pulposus Cells.

Oxid Med Cell Longev. 2020

[7]
Effect of allicin on wound healing: an experimental diabetes model.

J Wound Care. 2020-7-2

[8]
The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction.

Circ Res. 2020-7-31

[9]
Allicin alleviates inflammation of diabetic macroangiopathy via the Nrf2 and NF-kB pathway.

Eur J Pharmacol. 2020-6-5

[10]
Identification and antimicrobial activity evaluation of three peptides from laba garlic and the related mechanism.

Food Funct. 2019-6-26

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