PMID- 23840099
OWN - NLM
STAT- MEDLINE
DCOM- 20131203
LR  - 20211021
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2013
DP  - 2013
TI  - Nitric oxide is a mediator of antiproliferative effects induced by 
      proinflammatory cytokines on pancreatic beta cells.
PG  - 905175
LID - 10.1155/2013/905175 [doi]
LID - 905175
AB  - 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 beta 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-1 beta , IFN- gamma , and TNF- alpha on cultured 
      islet beta 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 beta 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 beta cell and is implicated in beta -cell proliferation impairment observed 
      early from initial stage of insulitis.
FAU - Quintana-Lopez, Laura
AU  - Quintana-Lopez L
AD  - Investigation Unit, Puerta del Mar Hospital, Cadiz, Spain.
FAU - Blandino-Rosano, Manuel
AU  - Blandino-Rosano M
FAU - Perez-Arana, Gonzalo
AU  - Perez-Arana G
FAU - Cebada-Aleu, Alberto
AU  - Cebada-Aleu A
FAU - Lechuga-Sancho, Alfonso
AU  - Lechuga-Sancho A
FAU - Aguilar-Diosdado, Manuel
AU  - Aguilar-Diosdado M
FAU - Segundo, Carmen
AU  - Segundo C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130612
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Body Weight/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cytokines/*pharmacology
MH  - Fluorescent Antibody Technique
MH  - Guanylate Cyclase/metabolism
MH  - Insulin-Secreting Cells/*cytology/drug effects
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1beta/pharmacology
MH  - Male
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/*pharmacology
MH  - Nitric Oxide Synthase/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - omega-N-Methylarginine/pharmacology
PMC - PMC3694487
EDAT- 2013/07/11 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/06/12
CRDT- 2013/07/11 06:00
PHST- 2013/02/26 00:00 [received]
PHST- 2013/05/21 00:00 [revised]
PHST- 2013/05/23 00:00 [accepted]
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/06/12 00:00 [pmc-release]
AID - 10.1155/2013/905175 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2013;2013:905175. doi: 10.1155/2013/905175. Epub 2013 Jun 12.