Modulation of intracellular signaling pathways in insulin-producing cells lines by INGAP-PP / Analise das vias de sinalização intracelulares em linhagens de celulas produtoras de insulina expostas ao INGAP-PP

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

The pentadecapeptide comprising the 104-118 aminoacid sequence of the ilotropin-derived Reg3- related islet neogenesis associated protein (INGA-PP) has been implicated in pancreatic beta-cell neogenesis and enhancement of the insulin secretion in pancreatic islets. There is little information regarding the mechanism of action of the polypeptide. The aim of this study was to investigate intracellular pathways by which INGAP-PP signs insulin-producing cells. The results show that INGAP-PP increased the insulin secretion and induced mobilization of intracellular calcium in MIN6 cells. INGAP-PP exposure activated c-Myc, serum response element (SRE) and particularly nuclear factor kappa B (NF?B) in both MIN6 and RINm5F insulin-producing cells. There was an increase in the proliferation rate of viable cells that was accompanied by an increase in the proliferating cell nuclear antigen (PCNA) protein expression following INGAP-PP treatment. In addition, INGAP-PP increased the expression of the muscarinic M3 receptor subtype. This effect was impaired by blocking NF?B signaling pathway. Cells incubated in the presence of foetal calf serum (FCS) also showed increased M3 receptor expression. In conclusion, these data show that activation of c-Myc signaling pathway and increased PCNA expression might be involved in the increased proliferation rate of insulin-producing cells following incubation with INGAP-PP. NF?B signaling plays an essential role in controlling the expression of the acetylcholine M3 receptor

ASSUNTO(S)

proliferação celular fatores de transcrição cell proliferation diabetes diabetes muscarinic receptors trasncription factors receptores muscarinicos ingap

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