Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo

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Standard

Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo. / Berchtold, Lukas A.; Miani, Michela; Diep, Thi A.; Madsen, Andreas N.; Cigliola, Valentina; Colli, Maikel; Krivokapic, Jelena M.; Pociot, Flemming; Eizirik, Decio L.; Meda, Paolo; Hoist, Birgitte; Billestrup, Nils; Storling, Joachim.

I: Molecular and Cellular Endocrinology, Bind 448, 2017, s. 108-121.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Berchtold, LA, Miani, M, Diep, TA, Madsen, AN, Cigliola, V, Colli, M, Krivokapic, JM, Pociot, F, Eizirik, DL, Meda, P, Hoist, B, Billestrup, N & Storling, J 2017, 'Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo', Molecular and Cellular Endocrinology, bind 448, s. 108-121. https://doi.org/10.1016/j.mce.2017.04.001

APA

Berchtold, L. A., Miani, M., Diep, T. A., Madsen, A. N., Cigliola, V., Colli, M., Krivokapic, J. M., Pociot, F., Eizirik, D. L., Meda, P., Hoist, B., Billestrup, N., & Storling, J. (2017). Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo. Molecular and Cellular Endocrinology, 448, 108-121. https://doi.org/10.1016/j.mce.2017.04.001

Vancouver

Berchtold LA, Miani M, Diep TA, Madsen AN, Cigliola V, Colli M o.a. Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo. Molecular and Cellular Endocrinology. 2017;448:108-121. https://doi.org/10.1016/j.mce.2017.04.001

Author

Berchtold, Lukas A. ; Miani, Michela ; Diep, Thi A. ; Madsen, Andreas N. ; Cigliola, Valentina ; Colli, Maikel ; Krivokapic, Jelena M. ; Pociot, Flemming ; Eizirik, Decio L. ; Meda, Paolo ; Hoist, Birgitte ; Billestrup, Nils ; Storling, Joachim. / Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo. I: Molecular and Cellular Endocrinology. 2017 ; Bind 448. s. 108-121.

Bibtex

@article{1d626142cf4f499ebb09d16652ee2beb,

title = "Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo",

abstract = "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 β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-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 β-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-βH1 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 β-cells.",

keywords = "Apoptosis, beta-cell, Cytokine, Insulin, Type 1 diabetes",

author = "Berchtold, {Lukas A.} and Michela Miani and Diep, {Thi A.} and Madsen, {Andreas N.} and Valentina Cigliola and Maikel Colli and Krivokapic, {Jelena M.} and Flemming Pociot and Eizirik, {Decio L.} and Paolo Meda and Birgitte Hoist and Nils Billestrup and Joachim Storling",

year = "2017",

doi = "10.1016/j.mce.2017.04.001",

language = "English",

volume = "448",

pages = "108--121",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo

AU - Berchtold, Lukas A.

AU - Miani, Michela

AU - Diep, Thi A.

AU - Madsen, Andreas N.

AU - Cigliola, Valentina

AU - Colli, Maikel

AU - Krivokapic, Jelena M.

AU - Pociot, Flemming

AU - Eizirik, Decio L.

AU - Meda, Paolo

AU - Hoist, Birgitte

AU - Billestrup, Nils

AU - Storling, Joachim

PY - 2017

Y1 - 2017

N2 - 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 β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-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 β-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-βH1 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 β-cells.

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 β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-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 β-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-βH1 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 β-cells.

KW - Apoptosis

KW - beta-cell

KW - Cytokine

KW - Insulin

KW - Type 1 diabetes

U2 - 10.1016/j.mce.2017.04.001

DO - 10.1016/j.mce.2017.04.001

M3 - Journal article

C2 - 28390953

VL - 448

SP - 108

EP - 121

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -

ID: 182540248