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

Sci Rep 2017 06 26;7(1):3994. Epub 2017 Jun 26.

DFG Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.

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 (HO), we reveal that glucose can directly increase the levels of HO. Furthermore, a moderate increase in HO levels can stimulate beta-cell proliferation. Interestingly, while high HO 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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http://dx.doi.org/10.1038/s41598-017-03873-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484671PMC
June 2017
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References

(Supplied by CrossRef)

GS Eisenbarth et al.
N Engl J Med 1986

M Prentki et al.
J Clin Invest 2006

RP Robertson et al.
J Biol Chem 2004

S Guo et al.
J Clin Invest 2013

J Pi et al.
Toxicol Appl Pharmacol 2010

YE Lee et al.
PLoS One 2012

H Mizukami et al.
Diabetes Care 2014

H Sakuraba et al.
Diabetologia 2002

JS Harmon et al.
Endocrinology 2009

H Kaneto et al.
Diabetes 1999

B Xu et al.
Free Radic Biol Med 1999

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