PMID- 29079704
OWN - NLM
STAT- MEDLINE
DCOM- 20180111
LR  - 20220409
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 67
IP  - 1
DP  - 2018 Jan
TI  - Mitochondrial Protein UCP2 Controls Pancreas Development.
PG  - 78-84
LID - 10.2337/db17-0118 [doi]
AB  - The mitochondrial carrier uncoupling protein (UCP) 2 belongs to the family of the 
      UCPs. Despite its name, it is now accepted that UCP2 is rather a metabolite 
      transporter than a UCP. UCP2 can regulate oxidative stress and/or energetic 
      metabolism. In rodents, UCP2 is involved in the control of alpha- and beta-cell mass as 
      well as insulin and glucagon secretion. Our aim was to determine whether the 
      effects of UCP2 observed on beta-cell mass have an embryonic origin. Thus, we used 
      Ucp2 knockout mice. We found an increased size of the pancreas in Ucp2(-/-) 
      fetuses at embryonic day 16.5, associated with a higher number of alpha- and beta-cells. 
      This phenotype was caused by an increase of PDX1(+) progenitor cells. 
      Perinatally, an increase in the proliferation of endocrine cells also 
      participates in their expansion. Next, we analyzed the oxidative stress in the 
      pancreata. We quantified an increased nuclear translocation of nuclear factor 
      erythroid 2-related factor 2 (NRF2) in the mutant, suggesting an increased 
      production of reactive oxygen species (ROS). Phosphorylation of AKT, an ROS 
      target, was also activated in the Ucp2(-/-) pancreata. Finally, administration of 
      the antioxidant N-acetyl-l-cysteine to Ucp2(-/-) pregnant mice alleviated the 
      effect of knocking out UCP2 on pancreas development. Together, these data 
      demonstrate that UCP2 controls pancreas development through the ROS-AKT signaling 
      pathway.
CI  - (c) 2017 by the American Diabetes Association.
FAU - Broche, Benjamin
AU  - Broche B
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Ben Fradj, Selma
AU  - Ben Fradj S
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Aguilar, Esther
AU  - Aguilar E
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Sancerni, Tiphaine
AU  - Sancerni T
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
AD  - Universite Paris Diderot, Sorbonne Paris Cite, Paris, France.
FAU - Benard, Matthieu
AU  - Benard M
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Makaci, Fatna
AU  - Makaci F
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Berthault, Claire
AU  - Berthault C
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Scharfmann, Raphael
AU  - Scharfmann R
AUID- ORCID: 0000-0001-7619-337X
AD  - INSERM, U1016, Institut Cochin, Paris, France.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Alves-Guerra, Marie-Clotilde
AU  - Alves-Guerra MC
AD  - INSERM, U1016, Institut Cochin, Paris, France bertrand.duvillie@curie.fr 
      clotilde.alves-guerra@inserm.fr.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
FAU - Duvillie, Bertrand
AU  - Duvillie B
AUID- ORCID: 0000-0003-0551-8100
AD  - INSERM, U1016, Institut Cochin, Paris, France bertrand.duvillie@curie.fr 
      clotilde.alves-guerra@inserm.fr.
AD  - CNRS, UMR8104, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171027
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Uncoupling Protein 2)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Glucagon-Secreting Cells/metabolism
MH  - Immunohistochemistry
MH  - Insulin-Secreting Cells/metabolism
MH  - Membrane Potential, Mitochondrial/genetics/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Pancreas/*enzymology/*metabolism
MH  - Phosphorylation/genetics/physiology
MH  - Polymerase Chain Reaction
MH  - Reactive Oxygen Species/metabolism
MH  - Uncoupling Protein 2/genetics/*metabolism
EDAT- 2017/10/29 06:00
MHDA- 2018/01/13 06:00
CRDT- 2017/10/29 06:00
PHST- 2017/01/27 00:00 [received]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2017/10/29 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2017/10/29 06:00 [entrez]
AID - db17-0118 [pii]
AID - 10.2337/db17-0118 [doi]
PST - ppublish
SO  - Diabetes. 2018 Jan;67(1):78-84. doi: 10.2337/db17-0118. Epub 2017 Oct 27.