ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1613081
This article is part of the Research TopicDoes Adult Beta Neogenesis Occur?View all 5 articles
Cdk5 mediates impaired autophagy by regulating NGF/Sirt1 axis to cause diabetic islet β cell damage
Provisionally accepted
Yuejia Tao1
Yipeng Liu2Shijie Hou3Lijun Tang2
Kai Wei2
Shanshan Zheng2Ying Zhang2Zunsong Wang2
Shunyao Liu2*- 1Department of Pathology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Nephrology, Shandong Lung Cancer Institute, Jinan, China
- 2Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Nephrology, Jinan, China
- 3Department of Nephrology, Ruijin-Hainan Hospital Shanghai Jiao Tong University School of Medicine (Hainan Boao Research Hospital), Qionghai, China
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Abstract: The number of patients with diabetes is increasing annually, and islet β cell damage plays a central role in the occurrence and development of diabetes. The activation of cyclin-dependent kinase 5 (Cdk5) is involved in the development of diabetes; however, its specific mechanism has not been fully elucidated. This study aimed to investigate the role of Cdk5 in diabetic islet β cell injury. Our results indicate that Cdk5 is upregulated in islet β cells under diabetic conditions, which results in impaired autophagy, and that its inhibition mitites islet β cell injury. In addition, high glucose decreased the levels of nerve growth factor (NGF) and Sirtuin 1 (Sirt1). NGF knockdown was associated with Sirt1 downregulation, while its overexpression upregulated Sirt1, restored autophagy, indicating that NGF positively regulates Sirt1 in islet β cells. Finally, we found that the NGF inhibitor K252a attenuated the protective effect of Lv-Cdk5 shRNA against high glucose-induced islet β cell injury in a mouse model. In conclusion, Cdk5 negatively regulates the NGF/Sirt1 axis, resulting in impaired autophagy of islet β cells under high glucose environments, which lead to islet β cell dysfunction. The Cdk5-NGF/Sirt1 axis may be a new target for the treatment of diabetes.
Keywords: CDK5, diabetes, NGF, SIRT1, Autophagy
Received: 16 Apr 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Tao, Liu, Hou, Tang, Wei, Zheng, Zhang, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shunyao Liu, 1690525415@qq.com
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