Cargando…

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....

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783713154848522240
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
work_keys_str_mv AT proniewskibartosz systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT baranna systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT kieronskarudekanna systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT surajprazmowskajoanna systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT buczekelzbieta systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT czamarakrzysztof systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT majkazuzanna systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT czyzynskacichonizabela systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT kwiatkowskigrzegorz systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT matyjaszczykgwardakarolina systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice
AT chlopickistefan systemicadministrationofinsulinreceptorantagonistresultsinendothelialandperivascularadiposetissuedysfunctioninmice