Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pan Liu, Zhengdong Zhang, Jinwu Wang, Xiao Zhang, Xiaoping Yu, Yao Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	empagliflozin pancreatic β cells nlrp3 caspase-1 gsdmd Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/629c10220c7c45bc9d859f365ef3aee2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:629c10220c7c45bc9d859f365ef3aee2
record_format	dspace
spelling	oai:doaj.org-article:629c10220c7c45bc9d859f365ef3aee22021-12-01T14:41:00ZEmpagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies2165-59792165-598710.1080/21655979.2021.2001240https://doaj.org/article/629c10220c7c45bc9d859f365ef3aee22021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2001240https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downregulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/Gasdermin D (GSDMD) pyroptosis-related inflammasome pathway in vitro and in vivo. In vivo, animals were separated into blank control (control, C57/bl6j wild-type mice), diabetes model (db/db mice, BKS-Leprem2Cd479/Gpt mice), and db/db mice+EMPA (db/db+EMPA) groups. In vitro, pancreatic β cells were separated into low glucose (control), high glucose (HG), and HG+EMPA groups. The db/db+EMPA group were administered empagliflozin at 10 mg/(kg·day) by gavage for six months. Histological changes in the pancreatic tissues were observed by hematoxylin-eosin staining, and levels of the pyroptosis-related inflammatory factors NLPR3, caspase-1, and GSDMD were measured by immunohistochemistry and immunofluorescence staining methods. The Cell Counting Kit-8 assay was used to detect the effect of different concentrations of glucose and empagliflozin on the proliferation of mouse insulinoma islet β (β TC-6) cells. NLRP3/caspase-1/GSDMD expression was assessed by western blotting and immunofluorescent labeling in the β TC-6 cells. The results showed that empagliflozin reduced the pathological changes and inflammatory cell infiltration in the pancreatic tissues of db/db mice. Furthermore, empagliflozin not only reduced the expression levels of NLRP3/caspase-1/GSDMD in vitro, but also reduced their expression levels in vivo. In summary, our data suggested that empagliflozin protects the pancreatic tissues from diabetes mellitus-induced injury by downregulating the NLRP3/caspase-1/GSDMD pyroptosis-related inflammasome pathway.Pan LiuZhengdong ZhangJinwu WangXiao ZhangXiaoping YuYao LiTaylor & Francis Grouparticleempagliflozinpancreatic β cellsnlrp3caspase-1gsdmdBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9356-9366 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	empagliflozin pancreatic β cells nlrp3 caspase-1 gsdmd Biotechnology TP248.13-248.65
spellingShingle	empagliflozin pancreatic β cells nlrp3 caspase-1 gsdmd Biotechnology TP248.13-248.65 Pan Liu Zhengdong Zhang Jinwu Wang Xiao Zhang Xiaoping Yu Yao Li Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
description	Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downregulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/Gasdermin D (GSDMD) pyroptosis-related inflammasome pathway in vitro and in vivo. In vivo, animals were separated into blank control (control, C57/bl6j wild-type mice), diabetes model (db/db mice, BKS-Leprem2Cd479/Gpt mice), and db/db mice+EMPA (db/db+EMPA) groups. In vitro, pancreatic β cells were separated into low glucose (control), high glucose (HG), and HG+EMPA groups. The db/db+EMPA group were administered empagliflozin at 10 mg/(kg·day) by gavage for six months. Histological changes in the pancreatic tissues were observed by hematoxylin-eosin staining, and levels of the pyroptosis-related inflammatory factors NLPR3, caspase-1, and GSDMD were measured by immunohistochemistry and immunofluorescence staining methods. The Cell Counting Kit-8 assay was used to detect the effect of different concentrations of glucose and empagliflozin on the proliferation of mouse insulinoma islet β (β TC-6) cells. NLRP3/caspase-1/GSDMD expression was assessed by western blotting and immunofluorescent labeling in the β TC-6 cells. The results showed that empagliflozin reduced the pathological changes and inflammatory cell infiltration in the pancreatic tissues of db/db mice. Furthermore, empagliflozin not only reduced the expression levels of NLRP3/caspase-1/GSDMD in vitro, but also reduced their expression levels in vivo. In summary, our data suggested that empagliflozin protects the pancreatic tissues from diabetes mellitus-induced injury by downregulating the NLRP3/caspase-1/GSDMD pyroptosis-related inflammasome pathway.
format	article
author	Pan Liu Zhengdong Zhang Jinwu Wang Xiao Zhang Xiaoping Yu Yao Li
author_facet	Pan Liu Zhengdong Zhang Jinwu Wang Xiao Zhang Xiaoping Yu Yao Li
author_sort	Pan Liu
title	Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
title_short	Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
title_full	Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
title_fullStr	Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
title_full_unstemmed	Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
title_sort	empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the nlrp3/caspase-1/gsdmd pathway in pancreatic β cells: in vitro and in vivo studies
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/629c10220c7c45bc9d859f365ef3aee2
work_keys_str_mv	AT panliu empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies AT zhengdongzhang empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies AT jinwuwang empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies AT xiaozhang empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies AT xiaopingyu empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies AT yaoli empagliflozinprotectsdiabeticpancreatictissuefromdamagebyinhibitingtheactivationofthenlrp3caspase1gsdmdpathwayinpancreaticbcellsinvitroandinvivostudies
_version_	1718404995456434176

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

Ejemplares similares