Cytokine-Induced Inhibition of Insulin Release from Mouse Pancreatic β-Cells Deficient in Inducible Nitric Oxide Synthase

2001 ◽  
Vol 281 (2) ◽  
pp. 396-403 ◽  
Author(s):  
Annika K. Andersson ◽  
Malin Flodström ◽  
Stellan Sandler
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Insulin Release ◽  
Inducible Nitric Oxide Synthase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Translational Control of Inducible Nitric Oxide Synthase by p38 MAPK in Islet β-Cells

2013 ◽  
Vol 27 (2) ◽  
pp. 336-349 ◽  
Author(s):  
Yurika Nishiki ◽  
Adeola Adewola ◽  
Masayuki Hatanaka ◽  
Andrew T. Templin ◽  
Bernhard Maier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
P38 Mapk ◽  
Inducible Nitric Oxide Synthase ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Cytokine Signaling ◽  
Β Cells ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Abstract The MAPKs are transducers of extracellular signals such as proinflammatory cytokines. In islet β-cells, cytokinesacutely activate expression of the Nos2 gene encoding inducible nitric oxide synthase (iNOS), which ultimately impairs insulin release. Because iNOS production can also be regulated posttranscriptionally, we asked whether MAPKs participate in posttranscriptional regulatory events in β-cells and primary islets in response to cytokine signaling. We show that cytokines acutely reduce cellular oxygen consumption rate and impair aconitase activity. Inhibition of iNOS with l-NMMA or inhibition of Nos2 mRNA translation with GC7 [an inhibitor of eukaryotic translation initiation factor 5A (eIF5A) activity] reversed these defects, as did inhibition of p38 MAPK by PD169316. Although inhibition of p38 had no effect on the nuclear translocation of nuclear factor κB or the abundance of Nos2 transcripts during the immediate period after cytokine exposure, its inhibition or knockdown resulted in significant reduction in iNOS protein, a finding suggestive of a permissive role for p38 in Nos2 translation. Polyribosomal profiling experiments using INS-1 β-cells revealed that Nos2 mRNA remained associated with polyribosomes in the setting of p38 inhibition, in a manner similar to that seen with blockade of translational elongation by cycloheximide. Consistent with a role in translational elongation, p38 activity is required in part for the activation of the translational factor eIF5A by promoting its hypusination. Our results suggest a novel signaling pathway in β-cells in which p38 MAPK promotes translation elongation of Nos2 mRNA via regulation of eIF5A hypusination.

scholarly journals Expression of islet inducible nitric oxide synthase and inhibition of glucose-stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27

2007 ◽  
Vol 292 (5) ◽  
pp. E1447-E1455 ◽  
Author(s):  
Saleem S. Qader ◽  
Javier Jimenez-Feltström ◽  
Mats Ekelund ◽  
Ingmar Lundquist ◽  
Albert Salehi
Keyword(s):  
Nitric Oxide ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Inducible Nitric Oxide Synthase ◽  
Cyclic Gmp ◽  
Inos Expression ◽  
Β Cells ◽  
Lipid Infusion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Chronic exposure of pancreatic islets to elevated plasma lipids (lipotoxicity) can lead to β-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase (iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to β-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive (nc)NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in β-cells.

289: Roles of Inducible Nitric Oxide Synthase in Voiding Function and Bladder Pain During Experimental Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 96-96
Author(s):  
Masayoshi Nomura ◽  
Hisae Nishii ◽  
Masato Tsutsui ◽  
Naohiro Fujimoto ◽  
Tetsuro Matsumoto
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Voiding Function ◽  
Bladder Pain ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide
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