Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells

Laura Quintana-Lopez, Manuel Blandino Rosano, Gonzalo Perez-Arana, Alberto Cebada-Aleu, Alfonso Lechuga-Sancho, Manuel Aguilar-Diosdado, Carmen Segundo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Nitric oxide (NO) is involved in several biological processes. In type 1 diabetes mellitus (T1DM), proinflammatory cytokines activate an inducible isoform of NOS (iNOS) in β cells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1) in the antiproliferative effect of proinflammatory cytokines IL-1β, IFN-γ, and TNF-α on cultured islet β cells and (2) during the insulitis stage prior to diabetes onset using the Biobreeding (BB) rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect on β cell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on cultured β cell and is implicated in β-cell proliferation impairment observed early from initial stage of insulitis.

Original languageEnglish (US)
Article number905175
JournalMediators of Inflammation
Volume2013
DOIs
StatePublished - Jul 19 2013
Externally publishedYes

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Insulin-Secreting Cells
Nitric Oxide
Cytokines
omega-N-Methylarginine
Cultured Cells
Type 1 Diabetes Mellitus
Islets of Langerhans
Protein Isoforms
Biological Phenomena
Nitric Oxide Donors
Guanylate Cyclase
Interleukin-1
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Quintana-Lopez, L., Blandino Rosano, M., Perez-Arana, G., Cebada-Aleu, A., Lechuga-Sancho, A., Aguilar-Diosdado, M., & Segundo, C. (2013). Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells. Mediators of Inflammation, 2013, [905175]. https://doi.org/10.1155/2013/905175

Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells. / Quintana-Lopez, Laura; Blandino Rosano, Manuel; Perez-Arana, Gonzalo; Cebada-Aleu, Alberto; Lechuga-Sancho, Alfonso; Aguilar-Diosdado, Manuel; Segundo, Carmen.

In: Mediators of Inflammation, Vol. 2013, 905175, 19.07.2013.

Research output: Contribution to journalArticle

Quintana-Lopez, L, Blandino Rosano, M, Perez-Arana, G, Cebada-Aleu, A, Lechuga-Sancho, A, Aguilar-Diosdado, M & Segundo, C 2013, 'Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells', Mediators of Inflammation, vol. 2013, 905175. https://doi.org/10.1155/2013/905175
Quintana-Lopez, Laura ; Blandino Rosano, Manuel ; Perez-Arana, Gonzalo ; Cebada-Aleu, Alberto ; Lechuga-Sancho, Alfonso ; Aguilar-Diosdado, Manuel ; Segundo, Carmen. / Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells. In: Mediators of Inflammation. 2013 ; Vol. 2013.
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