RGD Reference Report - Nitric oxide mediates the survival action of IGF-1 and insulin in pancreatic beta cells. - Rat Genome Database

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Nitric oxide mediates the survival action of IGF-1 and insulin in pancreatic beta cells.

Authors: Cahuana, GM  Tejedo, JR  Hmadcha, A  Ramirez, R  Cuesta, AL  Soria, B  Martin, F  Bedoya, FJ 
Citation: Cahuana GM, etal., Cell Signal. 2008 Feb;20(2):301-10. Epub 2007 Oct 12.
RGD ID: 7794789
Pubmed: PMID:18023142   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2007.10.001   (Journal Full-text)

Generation of low levels of nitric oxide (NO) contributes to beta cell survival in vitro. The purpose of this study was to explore the link between NO and the survival pathway triggered by insulin-like growth factor-1 (IGF-1) and insulin in insulin producing RINm5F cells and in pancreatic islets. Results show that exposure of cells to IGF-1/insulin protects against serum deprivation-induced apoptosis. This action is prevented with inhibitors of NO generation, PI3K and Akt. Moreover, transfection with the negative dominant form of the tyrosine kinase c-Src abrogates the effect of IGF-1 and insulin on DNA fragmentation. An increase in the expression level of NOS3 protein and in the enzyme activity is observed following exposure of serum-deprived RINm5F cells to IGF-1 and insulin. Phosphorylation of IRS-1, IRS-2 and to less extent IRS-3 takes place when serum-deprived RINm5F cells and rat pancreatic islets are exposed to either IGF-1, insulin, or diethylenetriamine nitric oxide adduct (DETA/NO). In human islets, IRS-1 and IRS-2 proteins are present and tyrosine phosphorylated upon exposure to IGF-1, insulin and DETA/NO. Both rat and human pancreatic islets undergo DNA fragmentation when cultured in serum-free medium and IGF-1, insulin and DETA/NO protect efficiently from this damage. We then conclude that generation of NO participates in the activation of survival pathways by IGF-1 and insulin in beta cells.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to growth factor stimulus  IEP 7794789insulin-like growth factor-1RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)


Additional Information