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

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 plasticit...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-06, Vol.7 (1), p.3994-12, Article 3994
Main Authors: Ahmed Alfar, Ezzaldin, Kirova, Dilyana, Konantz, Judith, Birke, Sarah, Mansfeld, Jörg, Ninov, Nikolay
Format: Article
Language:English
Subjects:
13
13/106
14
14/63
59
631/136/142
631/136/2091
631/80/2373
64
64/116
82
96
Antioxidants
Beta cells
Cell growth
Cell proliferation
Diabetes mellitus
Glucose
Homeostasis
Humanities and Social Sciences
Hydrogen peroxide
Insulin
Metabolism
multidisciplinary
Nutrients
Pancreas
Plasticity
Reactive oxygen species
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 2 O 2 ), we reveal that glucose can directly increase the levels of H 2 O 2 . Furthermore, a moderate increase in H 2 O 2 levels can stimulate beta-cell proliferation. Interestingly, while high H 2 O 2 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-03873-9