PMID- 28390953
OWN - NLM
STAT- MEDLINE
DCOM- 20171121
LR  - 20180921
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 448
DP  - 2017 Jun 15
TI  - Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis 
      in vitro and impairs glucose tolerance in vivo.
PG  - 108-121
LID - S0303-7207(17)30214-9 [pii]
LID - 10.1016/j.mce.2017.04.001 [doi]
AB  - Pannexins (Panx's) are membrane proteins involved in a variety of biological 
      processes, including cell death signaling and immune functions. The role and 
      functions of Panx's in pancreatic beta-cells remain to be clarified. Here, we show 
      Panx1 and Panx2 expression in isolated islets, primary beta-cells, and beta-cell lines. 
      The expression of Panx2, but not Panx1, was downregulated by interleukin-1beta 
      (IL-1beta) plus interferon-gamma (IFNgamma), two pro-inflammatory cytokines suggested to 
      contribute to beta-cell demise in type 1 diabetes (T1D). siRNA-mediated knockdown 
      (KD) of Panx2 aggravated cytokine-induced apoptosis in rat INS-1E cells and 
      primary rat beta-cells, suggesting anti-apoptotic properties of Panx2. An 
      anti-apoptotic function of Panx2 was confirmed in isolated islets from Panx2(-/-) 
      mice and in human EndoC-betaH1 cells. Panx2 KD was associated with increased 
      cytokine-induced activation of STAT3 and higher expression of inducible nitric 
      oxide synthase (iNOS). Glucose-stimulated insulin release was impaired in 
      Panx2(-/-) islets, and Panx2(-/-) mice subjected to multiple low-dose 
      Streptozotocin (MLDS) treatment, a model of T1D, developed more severe diabetes 
      compared to wild type mice. These data suggest that Panx2 is an important 
      regulator of the insulin secretory capacity and apoptosis in pancreatic beta-cells.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Berchtold, Lukas A
AU  - Berchtold LA
AD  - Copenhagen Diabetes Research Center, Pediatric Department, University Hospital 
      Herlev, Denmark; Department of Biomedical Sciences, University of Copenhagen, 
      Denmark.
FAU - Miani, Michela
AU  - Miani M
AD  - ULB Center for Diabetes Research, Universite Libre de Bruxelles, Belgium.
FAU - Diep, Thi A
AU  - Diep TA
AD  - Department of Neurosciences and Pharmacology, University of Copenhagen, Denmark.
FAU - Madsen, Andreas N
AU  - Madsen AN
AD  - Department of Neurosciences and Pharmacology, University of Copenhagen, Denmark.
FAU - Cigliola, Valentina
AU  - Cigliola V
AD  - Department of Genetic Medicine and Development, University of Geneva, 
      Switzerland.
FAU - Colli, Maikel
AU  - Colli M
AD  - ULB Center for Diabetes Research, Universite Libre de Bruxelles, Belgium.
FAU - Krivokapic, Jelena M
AU  - Krivokapic JM
AD  - Department of Biomedical Sciences, University of Copenhagen, Denmark.
FAU - Pociot, Flemming
AU  - Pociot F
AD  - Copenhagen Diabetes Research Center, Pediatric Department, University Hospital 
      Herlev, Denmark.
FAU - Eizirik, Decio L
AU  - Eizirik DL
AD  - ULB Center for Diabetes Research, Universite Libre de Bruxelles, Belgium.
FAU - Meda, Paolo
AU  - Meda P
AD  - Department of Cellular Physiology and Metabolism, University of Geneva, 
      Switzerland.
FAU - Holst, Birgitte
AU  - Holst B
AD  - Department of Neurosciences and Pharmacology, University of Copenhagen, Denmark.
FAU - Billestrup, Nils
AU  - Billestrup N
AD  - Department of Biomedical Sciences, University of Copenhagen, Denmark.
FAU - Storling, Joachim
AU  - Storling J
AD  - Copenhagen Diabetes Research Center, Pediatric Department, University Hospital 
      Herlev, Denmark. Electronic address: Joachim.stoerling.01@regionh.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170405
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Connexins)
RN  - 0 (Cytokines)
RN  - 0 (PANX2 protein, human)
RN  - 0 (Panx2 protein, mouse)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (pannexin 2, rat)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Connexins/*deficiency/metabolism
MH  - Cytokines/*pharmacology
MH  - Gene Knockdown Techniques
MH  - Glucose Intolerance/*metabolism/pathology
MH  - Humans
MH  - Hyperglycemia/pathology
MH  - Inflammation/pathology
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - STAT3 Transcription Factor/metabolism
MH  - Streptozocin
OTO - NOTNLM
OT  - Apoptosis
OT  - Cytokine
OT  - Insulin
OT  - Type 1 diabetes
OT  - beta-cell
EDAT- 2017/04/10 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/04/10 06:00
PHST- 2016/11/29 00:00 [received]
PHST- 2017/03/20 00:00 [revised]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/04/10 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/04/10 06:00 [entrez]
AID - S0303-7207(17)30214-9 [pii]
AID - 10.1016/j.mce.2017.04.001 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2017 Jun 15;448:108-121. doi: 10.1016/j.mce.2017.04.001. 
      Epub 2017 Apr 5.