liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes
Biomed Centre, Uppsala.
Biomed Centre, Uppsala.
Karolinska Institute, Stockholm.
Karolinska Institute, Stockholm.
Show others and affiliations
2012 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 5, 1535-1543 p.Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis  Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes. 

Methods  Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.

Results  Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O2 s−1 [mg protein]−1), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (−1.1 ± 0.1 pmol O2 s−1 [mg protein]−1). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).

Conclusions/interpretation  db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2012. Vol. 55, no 5, 1535-1543 p.
Keyword [en]
db/db mice, Kidney, Mitochondria, Type 2 diabetes, Uncoupling protein-2
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-77324DOI: 10.1007/s00125-012-2469-5ISI: 000302994600036OAI: diva2:526341

Funding Agencies|Swedish Research Council||Swedish Diabetes Foundation||Family Erling-Persson Foundation||European Commission|FP7-KBBE-2009245030|NIH/NIDDK|DK-07785|

Available from: 2012-05-11 Created: 2012-05-11 Last updated: 2013-10-16

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Palm, Fredrik
By organisation
Division of Drug ResearchFaculty of Health Sciences
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 60 hits
ReferencesLink to record
Permanent link

Direct link