par Berchtold, Lukas Adrian;Miani, MICHELA ;Diep, Thi A;Madsen, Andreas AN;Cigliola, Valentina;Colli, Maikel Luis ;Krivokapic, Jelena JM;Pociot, Flemming;Eizirik, Decio L. ;Meda, Paolo;Holst, Birgitte;Billestrup, N;Størling, Joachim
Référence Molecular and cellular endocrinology, 448, page (108-121)
Publication Publié, 2017-06
Référence Molecular and cellular endocrinology, 448, page (108-121)
Publication Publié, 2017-06
Article révisé par les pairs
Résumé : | 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. |