Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity.
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Publication Date
2017-06-26ICR Author
Author
Ahmed Alfar, E
Kirova, D
Konantz, J
Birke, S
Mansfeld, J
Ninov, N
Type
Journal Article
Metadata
Show full item recordAbstract
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 (H<sub>2</sub>O<sub>2</sub>), we reveal that glucose can directly increase the levels of H<sub>2</sub>O<sub>2</sub>. Furthermore, a moderate increase in H<sub>2</sub>O<sub>2</sub> levels can stimulate beta-cell proliferation. Interestingly, while high H<sub>2</sub>O<sub>2</sub> 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.
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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Subject
Cell Line
Animals
Animals, Genetically Modified
Zebrafish
Hydrogen Peroxide
Reactive Oxygen Species
Glucose
Cell Proliferation
Insulin-Secreting Cells
Cell Plasticity
Research team
Post-translational modifications and cell proliferation
Language
eng
Date accepted
2017-05-08
License start date
2017-06-26
Citation
Scientific reports, 2017, 7 (1), pp. 3994 - ?