Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice

被引:10
|
作者
Proniewski, Bartosz [1 ]
Bar, Anna [1 ]
Kieronska-Rudek, Anna [1 ,2 ]
Suraj-Prazmowska, Joanna [1 ]
Buczek, Elzbieta [1 ]
Czamara, Krzysztof [1 ]
Majka, Zuzanna [1 ,3 ]
Czyzynska-Cichon, Izabela [1 ]
Kwiatkowski, Grzegorz [1 ]
Matyjaszczyk-Gwarda, Karolina [1 ]
Chlopicki, Stefan [1 ,2 ]
机构
[1] Jagiellonian Univ, Jagiellonian Ctr Expt Therapeut JCET, Bobrzynskiego 14, PL-30348 Krakow, Poland
[2] Jagiellonian Univ Med Coll, Fac Pharmacol, Grzegorzecka 16, PL-31531 Krakow, Poland
[3] Jagiellonian Univ, Fac Chem, Gronostajowa 2, PL-30387 Krakow, Poland
关键词
endothelial function; magnetic resonance imaging; perivascular adipose tissue; insulin receptor antagonist; PROTEIN BIOMARKERS; VASODILATION; PERMEABILITY; PHARMACOLOGY; ADIPONECTIN; RESISTANCE; DELETION; MODEL;
D O I
10.3390/cells10061448
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:17
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