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

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...

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Autores principales:	Ezzaldin Ahmed Alfar, Dilyana Kirova, Judith Konantz, Sarah Birke, Jörg Mansfeld, Nikolay Ninov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a452e7b354d4495b8ea96d99c9042165
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spelling	oai:doaj.org-article:a452e7b354d4495b8ea96d99c90421652021-12-02T15:05:51ZDistinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity10.1038/s41598-017-03873-92045-2322https://doaj.org/article/a452e7b354d4495b8ea96d99c90421652017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03873-9https://doaj.org/toc/2045-2322Abstract 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.Ezzaldin Ahmed AlfarDilyana KirovaJudith KonantzSarah BirkeJörg MansfeldNikolay NinovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ezzaldin Ahmed Alfar Dilyana Kirova Judith Konantz Sarah Birke Jörg Mansfeld Nikolay Ninov Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
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.
format	article
author	Ezzaldin Ahmed Alfar Dilyana Kirova Judith Konantz Sarah Birke Jörg Mansfeld Nikolay Ninov
author_facet	Ezzaldin Ahmed Alfar Dilyana Kirova Judith Konantz Sarah Birke Jörg Mansfeld Nikolay Ninov
author_sort	Ezzaldin Ahmed Alfar
title	Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
title_short	Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
title_full	Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
title_fullStr	Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
title_full_unstemmed	Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
title_sort	distinct levels of reactive oxygen species coordinate metabolic activity with beta-cell mass plasticity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a452e7b354d4495b8ea96d99c9042165
work_keys_str_mv	AT ezzaldinahmedalfar distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity AT dilyanakirova distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity AT judithkonantz distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity AT sarahbirke distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity AT jorgmansfeld distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity AT nikolayninov distinctlevelsofreactiveoxygenspeciescoordinatemetabolicactivitywithbetacellmassplasticity
_version_	1718388662725509120

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

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