dc.contributor.author | Ahmed Alfar, E | |
dc.contributor.author | Kirova, D | |
dc.contributor.author | Konantz, J | |
dc.contributor.author | Birke, S | |
dc.contributor.author | Mansfeld, J | |
dc.contributor.author | Ninov, N | |
dc.date.accessioned | 2020-09-03T11:29:03Z | |
dc.date.issued | 2017-06-26 | |
dc.identifier.citation | Scientific reports, 2017, 7 (1), pp. 3994 - ? | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4061 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.doi | 10.1038/s41598-017-03873-9 | |
dc.description.abstract | The pancreatic beta-cells control glucose homeostasis by secreting insulin in response to nutrient intake. The number of beta-cells is under tight metabolic control, as this number increases with higher nutrient intake. However, the signaling pathways matching nutrition with beta-cell mass plasticity remain poorly defined. By applying pharmacological and genetic manipulations, we show that reactive oxygen species (ROS) regulate dose-dependently beta-cell proliferation in vivo and in vitro. In particular, reducing ROS levels in beta-cells blocks their proliferation in response to nutrients. Using a non-invasive genetic sensor of intracellular hydrogen peroxide (H2O2), we reveal that glucose can directly increase the levels of H2O2. Furthermore, a moderate increase in H2O2 levels can stimulate beta-cell proliferation. Interestingly, while high H2O2 levels are inhibitory to beta-cell proliferation, they expand beta-cell mass in vivo by inducing rapid beta-cell neogenesis. Our study thus reveals a ROS-level-dependent mechanism linking nutrients with beta-cell mass plasticity. Hence, given the requirement of ROS for beta-cell mass expansion, antioxidant therapies should be applied with caution in diabetes. | |
dc.format | Electronic | |
dc.format.extent | 3994 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line | |
dc.subject | Animals | |
dc.subject | Animals, Genetically Modified | |
dc.subject | Zebrafish | |
dc.subject | Hydrogen Peroxide | |
dc.subject | Reactive Oxygen Species | |
dc.subject | Glucose | |
dc.subject | Cell Proliferation | |
dc.subject | Insulin-Secreting Cells | |
dc.subject | Cell Plasticity | |
dc.title | Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-08 | |
rioxxterms.versionofrecord | 10.1038/s41598-017-03873-9 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-06-26 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Scientific reports | |
pubs.issue | 1 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Post-translational modifications and cell proliferation | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Post-translational modifications and cell proliferation | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Post-translational modifications and cell proliferation | |
dc.contributor.icrauthor | Mansfeld, Joerg | |