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Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the r...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025089/ https://www.ncbi.nlm.nih.gov/pubmed/35453472 http://dx.doi.org/10.3390/antiox11040788 |
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author | Petry, Sebastian Friedrich Römer, Axel Rawat, Divya Brunner, Lara Lerch, Nina Zhou, Mengmeng Grewal, Rekha Sharifpanah, Fatemeh Sauer, Heinrich Eckert, Gunter Peter Linn, Thomas |
author_facet | Petry, Sebastian Friedrich Römer, Axel Rawat, Divya Brunner, Lara Lerch, Nina Zhou, Mengmeng Grewal, Rekha Sharifpanah, Fatemeh Sauer, Heinrich Eckert, Gunter Peter Linn, Thomas |
author_sort | Petry, Sebastian Friedrich |
collection | PubMed |
description | Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion. |
format | Online Article Text |
id | pubmed-9025089 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90250892022-04-23 Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro Petry, Sebastian Friedrich Römer, Axel Rawat, Divya Brunner, Lara Lerch, Nina Zhou, Mengmeng Grewal, Rekha Sharifpanah, Fatemeh Sauer, Heinrich Eckert, Gunter Peter Linn, Thomas Antioxidants (Basel) Article Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion. MDPI 2022-04-15 /pmc/articles/PMC9025089/ /pubmed/35453472 http://dx.doi.org/10.3390/antiox11040788 Text en © 2022 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 Petry, Sebastian Friedrich Römer, Axel Rawat, Divya Brunner, Lara Lerch, Nina Zhou, Mengmeng Grewal, Rekha Sharifpanah, Fatemeh Sauer, Heinrich Eckert, Gunter Peter Linn, Thomas Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title | Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title_full | Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title_fullStr | Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title_full_unstemmed | Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title_short | Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro |
title_sort | loss and recovery of glutaredoxin 5 is inducible by diet in a murine model of diabesity and mediated by free fatty acids in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025089/ https://www.ncbi.nlm.nih.gov/pubmed/35453472 http://dx.doi.org/10.3390/antiox11040788 |
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