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Type: Artigo de periódico
Title: Requirement of NF-kappaB signalling pathway for modulation of the cholinergic muscarinic M-3 receptor expression by INGAP-PP in insulin-producing cells
Author: Paula, FMM
Barbosa, HCL
Carneiro, EM
Persaud, SJ
Gagliardino, JJ
Boschero, AC
Souza, KLA
Abstract: The pentadecapeptide comprising the 104-118 amino acid sequence of the ilotropin-derived Reg3-related islet neogenesis-associated protein (INGAP-PP) has been implicated in beta cell neogenesis and enhancement of insulin secretion in pancreatic islets. The aim of this study was to investigate intracellular pathways by which INGAP-PP signals in insulin-producing cells. Treatment with INGAP-PP increased insulin secretion and intracellular calcium levels in MIN6 cells. INGAP-PP exposure activated c-Myc, serum and particularly nuclear factor-kappaB (NF-kappa B) response elements in insulin-producing cells (1.7 +/- 0.1, 1.8 +/- 0.1, 2.4 +/- 0.3 for RINm5F, and 1.3 +/- 0.1, 1.3 +/- 0.1 and 1.6 +/- 0.1 fold for MIN6 cells compared to controls, respectively). There was an increase in the proliferation rate of viable cells (162 +/- 17% for RINm5F and 155 13% for MIN6) that was accompanied by an increase in proliferating cell nuclear antigen (PCNA) protein expression (187 +/- 19% and 170 +/- 8% for RINm5F and MIN6 cells respectively) following INGAP-PP treatment. INGAP-PP increased the expression of the muscarinic M-3 receptor subtype (169 +/- 4% for RINm5F and 222 +/- 20% for MIN6 cells). Activation of multiple serum response elements by foetal calf serum also increased muscarinic M-3 receptor expression (173 +/- 9% for RINm5F and 140 +/- 7% for MIN6 cells). The blockade of NF-kappa B signalling pathway strongly decreased muscarinic M-3 receptor expression in response to both stimuli. In summary, a network of intracellular signals that includes activation of c-Myc signalling pathway and increased PCNA expression might be related to the increased proliferation rate of insulin-producing cells following incubation with INGAP-PP. NF-kappa B signalling plays an essential role in controlling the expression of the muscarinic M-3 receptor. (C) 2010 Elsevier B.V. All rights reserved.
Subject: Diabetes
Cholinergic receptor
Transcription factor
Gene expression regulation
Country: Holanda
Editor: Elsevier Science Bv
Citation: European Journal Of Pharmacology. Elsevier Science Bv, v. 642, n. 41699, n. 37, n. 46, 2010.
Rights: fechado
Identifier DOI: 10.1016/j.ejphar.2010.05.056
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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