uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
2015 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 49, no 11, 1308-1318 p.Article in journal (Refereed) Published
Abstract [en]

In type 2 diabetes, it has been proposed that pancreatic beta-cell dysfunction is promoted by oxidative stress caused by NADPH oxidase (NOX) overactivity. Five different NOX enzymes (NOX1-5) have been characterized, among which NOX1 and NOX2 have been proposed to negatively affect beta-cells, but the putative role of NOX4 in type 2 diabetes-associated beta-cell dysfunction and glucose intolerance is largely unknown. Therefore, we presently investigated the importance of NOX4 for high-fat diet or HFD-induced glucose intolerance using male C57BL/6 mice using the new NOX4 inhibitor GLX351322, which has relative NOX4 selectivity over NOX2. In HFD-treated male C57BL/6 mice a two-week treatment with GLX351322 counteracted non-fasting hyperglycemia and impaired glucose tolerance. This effect occurred without any change in peripheral insulin sensitivity. To ascertain that NOX4 also plays a role for the function of human beta-cells, we observed that glucose- and sodium palmitate-induced insulin release from human islets in vitro was increased in response to NOX4 inhibitors. In long-term experiments (1-3 days), high-glucose-induced human islet cell reactive oxygen species (ROS) production and death were prevented by GLX351322. We propose that while short-term NOX4-generated ROS production is a physiological requirement for beta-cell function, persistent NOX4 activity, for example, during conditions of high-fat feeding, promotes ROS-mediated beta-cell dysfunction. Thus, selective NOX inhibition may be a therapeutic strategy in type 2 diabetes.

Place, publisher, year, edition, pages
2015. Vol. 49, no 11, 1308-1318 p.
Keyword [en]
NOX inhibitor; human islet; reactive oxygen radical; NADPH oxidase; insulin release; beta-cell death; glucose intolerance
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-273312DOI: 10.3109/10715762.2015.1067697ISI: 000369892600003PubMedID: 26118714OAI: oai:DiVA.org:uu-273312DiVA: diva2:894708
Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2017-11-30Bibliographically approved

Open Access in DiVA

fulltext(2954 kB)127 downloads
File information
File name FULLTEXT01.pdfFile size 2954 kBChecksum SHA-512
1e205721eb1f9b9bf3a6915ad95462da7d27c8be6807216681d63e61f1984a7cf9f0374078385735d8ecb20e39d997c86caa024f6aebc9d0465b873a6a23d614
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Anvari, EbrahimWelsh, Nils

Search in DiVA

By author/editor
Anvari, EbrahimWelsh, Nils
By organisation
Department of Medical Cell BiologyScience for Life Laboratory, SciLifeLab
In the same journal
Free radical research
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 127 downloads
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

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 609 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf