Sökning: onr:"swepub:oai:DiVA.org:uu-361674" >
Deletion of Uncoupl...
Deletion of Uncoupling Protein-2 reduces renal mitochondrial leak respiration, intrarenal hypoxia and proteinuria in a mouse model of type 1 diabetes
-
- Friederich, Malou, 1983- (författare)
- Uppsala universitet,Integrativ Fysiologi
-
- Persson, Patrik (författare)
- Uppsala universitet,Integrativ Fysiologi
-
- Hansell, Peter (författare)
- Uppsala universitet,Integrativ Fysiologi
-
visa fler...
-
- Palm, Fredrik, 1973- (författare)
- Uppsala universitet,Integrativ Fysiologi
-
visa färre...
-
(creator_code:org_t)
- 2018-03-15
- 2018
- Engelska.
-
Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 223:4
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- AimUncoupling protein-2 (UCP-2) can induce mitochondrial uncoupling in the diabetic kidney. Although mitochondrial uncoupling reduces oxidative stress originating from the mitochondria and can be regarded as a protective mechanism, the increased oxygen consumption occurring secondarily to increased mitochondria uncoupling, that is leak respiration, may contribute to kidney tissue hypoxia. Using UCP-2(-/-) mice, we tested the hypothesis that UCP-2-mediated leak respiration is important for the development of diabetes-induced intrarenal hypoxia and proteinuria. MethodsKidney function, invivo oxygen metabolism, urinary protein leakage and mitochondrial function were determined in wild-type and UCP-2(-/-) mice during normoglycaemia and 2weeks after diabetes induction. ResultsDiabetic wild-type mice displayed mitochondrial leak respiration, pronounced intrarenal hypoxia, proteinuria and increased urinary KIM-1 excretion. However, diabetic UCP-2(-/-) mice did not develop increased mitochondrial leak respiration and presented with normal intrarenal oxygen levels, urinary protein and KIM-1 excretion. ConclusionAlthough functioning as an antioxidant system, mitochondria uncoupling is always in co-occurrence with increased oxygen consumption, that is leak respiration; a potentially detrimental side effect as it can result in kidney tissue hypoxia; an acknowledged unifying pathway to nephropathy. Indeed, this study demonstrates a novel mechanism in which UCP-2-mediated mitochondrial leak respiration is necessary for the development of diabetes-induced intrarenal tissue hypoxia and proteinuria.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- diabetic nephropathy
- kidney
- kidney injury molecule-1
- mitochondria
- oxygen consumption
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas