Title |
Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
|
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Published in |
Scientific Reports, June 2017
|
DOI | 10.1038/s41598-017-03873-9 |
Pubmed ID | |
Authors |
Ezzaldin Ahmed Alfar, Dilyana Kirova, Judith Konantz, Sarah Birke, Jörg Mansfeld, Nikolay Ninov |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 60 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 21 | 35% |
Student > Master | 11 | 18% |
Researcher | 5 | 8% |
Student > Doctoral Student | 4 | 7% |
Student > Bachelor | 4 | 7% |
Other | 6 | 10% |
Unknown | 9 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 30 | 50% |
Agricultural and Biological Sciences | 10 | 17% |
Medicine and Dentistry | 3 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Engineering | 2 | 3% |
Other | 2 | 3% |
Unknown | 11 | 18% |