TFP5 attenuates cyclin-dependent kinase 5-mediated islet β-cell damage in diabetes
© 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd..
Islet β-cell damage and dysfunction represent the pathophysiological basis of diabetes. Excessive activation of cyclin-dependent kinase 5 (CDK5) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), although the exact mechanism remains unclear. Therefore, this study investigated the role of a CDK5 inhibitor (TFP5) in islet β-cell damage under diabetic conditions by regulating the expression of CDK5 in vitro and in vivo. CDK5 was upregulated under high glucose conditions in vivo and in vitro, which resulted in inflammation, oxidative stress, and apoptosis of islet β-cells, thereby decreasing insulin secretion. However, TFP5 treatment inhibited the overexpression of CDK5; reduced the inflammatory response, oxidative stress, and apoptosis of islet β cells; and restored insulin secretion. In conclusion, CDK5 is involved in islet β-cell damage under high glucose conditions, and TFP5 may represent a promising candidate for the development of treatments for T2DM.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:102 |
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| Enthalten in: |
Chemical biology & drug design - 102(2023), 1 vom: 04. Juli, Seite 76-87 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Shunyao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.06.2023 Date Revised 22.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cbdd.14235 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM355099446 |
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| 520 | |a © 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd. | ||
| 520 | |a Islet β-cell damage and dysfunction represent the pathophysiological basis of diabetes. Excessive activation of cyclin-dependent kinase 5 (CDK5) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), although the exact mechanism remains unclear. Therefore, this study investigated the role of a CDK5 inhibitor (TFP5) in islet β-cell damage under diabetic conditions by regulating the expression of CDK5 in vitro and in vivo. CDK5 was upregulated under high glucose conditions in vivo and in vitro, which resulted in inflammation, oxidative stress, and apoptosis of islet β-cells, thereby decreasing insulin secretion. However, TFP5 treatment inhibited the overexpression of CDK5; reduced the inflammatory response, oxidative stress, and apoptosis of islet β cells; and restored insulin secretion. In conclusion, CDK5 is involved in islet β-cell damage under high glucose conditions, and TFP5 may represent a promising candidate for the development of treatments for T2DM | ||
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| 700 | 1 | |a Li, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Danna |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Yuejia |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Guoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Shilu |e verfasserin |4 aut | |
| 700 | 1 | |a E, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yali |e verfasserin |4 aut | |
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