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Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice
Hyperglycemia linked to diabetes results in endothelial dysfunction. In the present work, we comprehensively characterized effects of short-term hyperglycemia induced by administration of an insulin receptor antagonist, the S961 peptide, on endothelium and perivascular adipose tissue (PVAT) in mice....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230211/ https://www.ncbi.nlm.nih.gov/pubmed/34207844 http://dx.doi.org/10.3390/cells10061448 |
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author | Proniewski, Bartosz Bar, Anna Kieronska-Rudek, Anna Suraj-Prażmowska, Joanna Buczek, Elżbieta Czamara, Krzysztof Majka, Zuzanna Czyzynska-Cichon, Izabela Kwiatkowski, Grzegorz Matyjaszczyk-Gwarda, Karolina Chlopicki, Stefan |
author_facet | Proniewski, Bartosz Bar, Anna Kieronska-Rudek, Anna Suraj-Prażmowska, Joanna Buczek, Elżbieta Czamara, Krzysztof Majka, Zuzanna Czyzynska-Cichon, Izabela Kwiatkowski, Grzegorz Matyjaszczyk-Gwarda, Karolina Chlopicki, Stefan |
author_sort | Proniewski, Bartosz |
collection | PubMed |
description | Hyperglycemia linked to diabetes results in endothelial dysfunction. In the present work, we comprehensively characterized effects of short-term hyperglycemia induced by administration of an insulin receptor antagonist, the S961 peptide, on endothelium and perivascular adipose tissue (PVAT) in mice. Endothelial function of the thoracic and abdominal aorta in 12-week-old male C57Bl/6Jrj mice treated for two weeks with S961 infusion via osmotic pumps was assessed in vivo using magnetic resonance imaging and ex vivo by detection of nitric oxide (NO) production using electron paramagnetic resonance spectroscopy. Additional methods were used to analyze PVAT, aortic segments and endothelial-specific plasma biomarkers. Systemic disruption of insulin signaling resulted in severe impairment of NO-dependent endothelial function and a loss of vasoprotective function of PVAT affecting the thoracic as well as abdominal parts of the aorta, however a fall in adiponectin expression and decreased uncoupling protein 1-positive area were more pronounced in the thoracic aorta. Results suggest that dysfunctional PVAT contributes to vascular pathology induced by altered insulin signaling in diabetes, in the absence of fat overload and obesity. |
format | Online Article Text |
id | pubmed-8230211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82302112021-06-26 Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice Proniewski, Bartosz Bar, Anna Kieronska-Rudek, Anna Suraj-Prażmowska, Joanna Buczek, Elżbieta Czamara, Krzysztof Majka, Zuzanna Czyzynska-Cichon, Izabela Kwiatkowski, Grzegorz Matyjaszczyk-Gwarda, Karolina Chlopicki, Stefan Cells Article Hyperglycemia linked to diabetes results in endothelial dysfunction. In the present work, we comprehensively characterized effects of short-term hyperglycemia induced by administration of an insulin receptor antagonist, the S961 peptide, on endothelium and perivascular adipose tissue (PVAT) in mice. Endothelial function of the thoracic and abdominal aorta in 12-week-old male C57Bl/6Jrj mice treated for two weeks with S961 infusion via osmotic pumps was assessed in vivo using magnetic resonance imaging and ex vivo by detection of nitric oxide (NO) production using electron paramagnetic resonance spectroscopy. Additional methods were used to analyze PVAT, aortic segments and endothelial-specific plasma biomarkers. Systemic disruption of insulin signaling resulted in severe impairment of NO-dependent endothelial function and a loss of vasoprotective function of PVAT affecting the thoracic as well as abdominal parts of the aorta, however a fall in adiponectin expression and decreased uncoupling protein 1-positive area were more pronounced in the thoracic aorta. Results suggest that dysfunctional PVAT contributes to vascular pathology induced by altered insulin signaling in diabetes, in the absence of fat overload and obesity. MDPI 2021-06-09 /pmc/articles/PMC8230211/ /pubmed/34207844 http://dx.doi.org/10.3390/cells10061448 Text en © 2021 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 Proniewski, Bartosz Bar, Anna Kieronska-Rudek, Anna Suraj-Prażmowska, Joanna Buczek, Elżbieta Czamara, Krzysztof Majka, Zuzanna Czyzynska-Cichon, Izabela Kwiatkowski, Grzegorz Matyjaszczyk-Gwarda, Karolina Chlopicki, Stefan Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title | Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title_full | Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title_fullStr | Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title_full_unstemmed | Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title_short | Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice |
title_sort | systemic administration of insulin receptor antagonist results in endothelial and perivascular adipose tissue dysfunction in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230211/ https://www.ncbi.nlm.nih.gov/pubmed/34207844 http://dx.doi.org/10.3390/cells10061448 |
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