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Metformin attenuate...
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Christensen, MichaelAarhus Univ, Dept Clin Med, Aarhus, Denmark
(författare)
Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein-2
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2018-11-08
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WILEY,2019
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-377680
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-377680URI
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https://doi.org/10.1002/dmrr.3091DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154567URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|Lundbeck Foundation; Swedish Research Council Medicine and Health; Family Ernfors Foundation; Swedish Diabetes Foundation; Danish Diabetes Academy
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Background: The purpose of the study is to examine the effect of metformin on oxygen metabolism and mitochondrial function in the kidney of an animal model of insulinopenic diabetes in order to isolate any renoprotective effect from any concomitant effect on blood glucose homeostasis.Methods: Sprague-Dawley rats were injected with streptozotocin (STZ) (50 mg kg(-1)) and when stable started on metformin treatment (250 mg kg(-1)) in the drinking water. Rats were prepared for in vivo measurements 25 to 30 days after STZ injection, where renal function, including glomerular filtration rate and sodium transport, was estimated in anesthetized rats. Intrarenal oxygen tension was measured using oxygen sensors. Furthermore, mitochondrial function was assessed in mitochondria isolated from kidney cortex and medulla analysed by high-resolution respirometry, and superoxide production was evaluated using electron paramagnetic resonance.Results: Insulinopenic rats chronically treated with metformin for 4 weeks displayed improved medullary tissue oxygen tension despite of no effect of metformin on blood glucose homeostasis. Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats.Conclusions: Metformin attenuates diabetes-induced renal medullary tissue hypoxia in an animal model of insulinopenic type 1 diabetes. The results suggest that the mechanistic pathway to attenuate the diabetes-induced medullary hypoxia is independent of blood glucose homeostasis and includes reduced UCP2-mediated mitochondrial proton LEAK.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Schiffer, Tomas A.Uppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala Univ, Sweden(Swepub:uu)tomsh655
(författare)
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Gustafsson, HåkanLinköpings universitet,Avdelningen för radiologiska vetenskaper,Medicinska fakulteten,Region Östergötland, Röntgenkliniken i Norrköping(Swepub:liu)hakgu16
(författare)
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Krag, Sören PalmelundAarhus Univ Hosp, Dept Pathol, Aarhus, Denmark
(författare)
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Nörregaard, RikkeAarhus Univ, Dept Clin Med, Aarhus, Denmark
(författare)
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Palm, Fredrik,1973-Uppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala Univ, Sweden(Swepub:uu)fredpalm
(författare)
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Aarhus Univ, Dept Clin Med, Aarhus, DenmarkInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes/Metabolism Research Reviews: WILEY35:21520-75521520-7560
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