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Adenosine A(2)a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress
Uppsala University, Sweden.
Uppsala University, Sweden.
Uppsala University, Sweden.
Uppsala University, Sweden.
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2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 214, no 3, 311-318 p.Article in journal (Refereed) Published
Abstract [en]

AimDiabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A(2a) receptor (A(2a)AR) protects kidney function in insulinopenic diabetic rats. MethodsStreptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A(2a)AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers. ResultsGlomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A(2a)AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A(2a)AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A(2a)AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF- and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness. ConclusionChronic A(2a)AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.

Place, publisher, year, edition, pages
Wiley: 12 months , 2015. Vol. 214, no 3, 311-318 p.
Keyword [en]
CGS21680; diabetes mellitus; diabetic nephropathy; kidney; macrophages; tumour necrosis factor-alpha
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-120031DOI: 10.1111/apha.12511ISI: 000356306300007PubMedID: 25891445OAI: oai:DiVA.org:liu-120031DiVA: diva2:840037
Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2015-07-06

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Palm, Fredrik
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Division of Drug ResearchFaculty of Medicine and Health Sciences
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