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Irisin attenuates pyroptosis in high glucose-induced pancreatic beta cells via the miR-133a-3p/FOXO1 axis
Affiliations- Department of Geriatric Medicine, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
open access
Abstract
Introduction: Irisin is closely related to type 2 diabetes mellitus (T2DM) and other metabolic diseases. It can improve the homeostasis of T2DM. MiR-133a-3p is decreased in the peripheral blood of patients with T2DM. Forkhead box protein O1 (FOXO1) is widely expressed in beta-cells and affects the occurrence of diabetes through transcriptional regulation and signalling pathway regulation.
Material and methods: The miR-133a-3p inhibitor was constructed to verify the effect of irisin on pyroptosis through miR-133a-3p. Next, we predicted the presence of targeted binding sequences between FOXO1 and miR-133a-3p by bioinformatics software, which was then confirmed with a double fluorescence assay. Finally, the FOXO1 overexpression vector was used to further verify the effect of irisin through the miR-133a-3p/FOXO1 axis.
Results: We first observed that irisin inhibited the protein levels of N-terminal gasdermin D (GSDMD-N) and cleaved caspase-1 and the secretion of interleukins (IL): IL-1beta and IL-18 in Min6 cells treated with high glucoes (HG). Irisin inhibited pyroptosis of Min6 cells treated with HG by reinforcing miR-133a-3p. Then, FOXO1 was validated to be the target gene of miR-133a. Both miR-133a-3p inhibitor and overexpression of FOXO1 restrained the force of irisin on pyroptosis in HG-induced Min6 cells.
Conclusion: We explored the protective effect of irisin on HG-induced pyroptosis of islet b-cells in vitro and explained its mechanism of inhibiting pyroptosis through the miR-133a-3p/FOXO1 axis, to provide a theoretical basis for finding new molecular targets to delay beta-cell failure and the treatment of T2DM.
Abstract
Introduction: Irisin is closely related to type 2 diabetes mellitus (T2DM) and other metabolic diseases. It can improve the homeostasis of T2DM. MiR-133a-3p is decreased in the peripheral blood of patients with T2DM. Forkhead box protein O1 (FOXO1) is widely expressed in beta-cells and affects the occurrence of diabetes through transcriptional regulation and signalling pathway regulation.
Material and methods: The miR-133a-3p inhibitor was constructed to verify the effect of irisin on pyroptosis through miR-133a-3p. Next, we predicted the presence of targeted binding sequences between FOXO1 and miR-133a-3p by bioinformatics software, which was then confirmed with a double fluorescence assay. Finally, the FOXO1 overexpression vector was used to further verify the effect of irisin through the miR-133a-3p/FOXO1 axis.
Results: We first observed that irisin inhibited the protein levels of N-terminal gasdermin D (GSDMD-N) and cleaved caspase-1 and the secretion of interleukins (IL): IL-1beta and IL-18 in Min6 cells treated with high glucoes (HG). Irisin inhibited pyroptosis of Min6 cells treated with HG by reinforcing miR-133a-3p. Then, FOXO1 was validated to be the target gene of miR-133a. Both miR-133a-3p inhibitor and overexpression of FOXO1 restrained the force of irisin on pyroptosis in HG-induced Min6 cells.
Conclusion: We explored the protective effect of irisin on HG-induced pyroptosis of islet b-cells in vitro and explained its mechanism of inhibiting pyroptosis through the miR-133a-3p/FOXO1 axis, to provide a theoretical basis for finding new molecular targets to delay beta-cell failure and the treatment of T2DM.
Keywords
irisin; T2DM; FOXO1; miR-133a-3p; pyroptosis
About this articleTitle
Irisin attenuates pyroptosis in high glucose-induced pancreatic beta cells via the miR-133a-3p/FOXO1 axis
Journal
Issue
Article type
Original paper
Pages
277-284
Published online
2023-05-15
Page views
1538
Article views/downloads
495
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2023;74(3):277-284.
Keywords
irisin
T2DM
FOXO1
miR-133a-3p
pyroptosis
Authors
Anjun Tan
Tianrong Li
Jingjing Yang
Jinwen Yu
Hewen Chen
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