Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1785081367648796672 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10385282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hanming luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT luyuting luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT taoyunhua luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT zhangxinwen luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT daichengqiu luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT zhangbingqian luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT xuhonghong luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance AT lijingya luteolinprotectspancreaticbcellsagainstapoptosisthroughregulationofautophagyandrosclearance |