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Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance

Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved...

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Autores principales: Han, Ming, Lu, Yuting, Tao, Yunhua, Zhang, Xinwen, Dai, Chengqiu, Zhang, Bingqian, Xu, Honghong, Li, Jingya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385282/
https://www.ncbi.nlm.nih.gov/pubmed/37513887
http://dx.doi.org/10.3390/ph16070975
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author Han, Ming
Lu, Yuting
Tao, Yunhua
Zhang, Xinwen
Dai, Chengqiu
Zhang, Bingqian
Xu, Honghong
Li, Jingya
author_facet Han, Ming
Lu, Yuting
Tao, Yunhua
Zhang, Xinwen
Dai, Chengqiu
Zhang, Bingqian
Xu, Honghong
Li, Jingya
author_sort Han, Ming
collection PubMed
description Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating β cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of β cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of β cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in β cells, possibly improving β cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of β cells. We also reveal some of the underlying mechanisms of luteolin’s cytoprotective function.
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spelling pubmed-103852822023-07-30 Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance Han, Ming Lu, Yuting Tao, Yunhua Zhang, Xinwen Dai, Chengqiu Zhang, Bingqian Xu, Honghong Li, Jingya Pharmaceuticals (Basel) Article Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating β cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of β cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of β cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in β cells, possibly improving β cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of β cells. We also reveal some of the underlying mechanisms of luteolin’s cytoprotective function. MDPI 2023-07-07 /pmc/articles/PMC10385282/ /pubmed/37513887 http://dx.doi.org/10.3390/ph16070975 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Ming
Lu, Yuting
Tao, Yunhua
Zhang, Xinwen
Dai, Chengqiu
Zhang, Bingqian
Xu, Honghong
Li, Jingya
Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title_full Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title_fullStr Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title_full_unstemmed Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title_short Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance
title_sort luteolin protects pancreatic β cells against apoptosis through regulation of autophagy and ros clearance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385282/
https://www.ncbi.nlm.nih.gov/pubmed/37513887
http://dx.doi.org/10.3390/ph16070975
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