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Sci Rep. 2017 Jun 26;7(1):3994. doi: 10.1038/s41598-017-03873-9.

Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity.

Author information

1
DFG Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
2
Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Hospital and Faculty of Medicine Carl Gustav Carus of Technische Universität Dresden, Dresden, Germany.
3
German Center for Diabetes Research (DZD e.V.), Neuherberg, Neuherberg, Germany.
4
Department of Pharmacology and Toxicology, Technische Universität Dresden, Dresden, Germany.
5
Cell Cycle, Biotechnology Center, Technische Universität Dresden, 01307, Dresden, Germany.
6
Cell Cycle, Biotechnology Center, Technische Universität Dresden, 01307, Dresden, Germany. nikolay.ninov@crt-dresden.de.
7
DFG Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany. joerg.mansfeld@tu-dresden.de.
8
Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Hospital and Faculty of Medicine Carl Gustav Carus of Technische Universität Dresden, Dresden, Germany. joerg.mansfeld@tu-dresden.de.
9
German Center for Diabetes Research (DZD e.V.), Neuherberg, Neuherberg, Germany. joerg.mansfeld@tu-dresden.de.

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.

PMID:
28652605
PMCID:
PMC5484671
DOI:
10.1038/s41598-017-03873-9
[Indexed for MEDLINE]
Free PMC Article

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