Maturation of the secretory response to glucose by INGAP (Islet Neongenesis Associated Protein) in islets of Langerhans of neonatal rats / Maturação da resposta secretoria a glicose pelo INGAP (Islet Neongenesis Associated Protein) em ilhotas de Langerhans de ratos neonatos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

The Islet Neogenesis Associated Protein (INGAP) increases pancreatic ß-cell mass and potentiates glucose-induced insulin secretion. Here, we have studied the effects of the pentadecapeptide having the 104-118 amino acid sequence of INGAP (INGAP-PP) on the expression of genes related to the pancreatic islets, the expression and phosphorylation of components of the PI3K and MAPK pathways, the cholinergic signaling, and static and dynamic insulin secretion in neonatal rat islet. Islets cultured with INGAP-PP released significantly more insulin in response to glucose than controls. The macroarray analysis showed that 210 out of 2,352 genes, spotted in the nylon membranes, were up- ,regulated while only 4 were down-regulated by INGAP-PP-treatment. The main categories of genes modulated by INGAP-PP 4-days cultured islet include several genes related with islet metabolism, insulin secretion mechanism, growth, maturation, maintenance of islet-cell mass, and exocytosis. Shortterm exposure of neonatal islets to INGAP-PP significantly increased Akt-Ser473 and ERK1/2-Thr202/Tyr204 phosphorylation as well as insulin secretion from islets perifused with 2 and 20 mM glucose. Four-days cultured islets with INGAP-PP also showed increased expression of M3 receptor subtype and PLC-ß2 proteins. In addition, brief exposure of INGAP-PP-treated islets to Cch significantly increased P70S6KThr389 and ERK1/2 phosphorylation and these islets released more insulin when challenged with Cch. In conclusion, these data show that INGAP-PP enhances insulin secretion and transcription of several islet genes, and also increases the expression and phosphorylation of proteins involved in PI3K and MAPK pathways. The increased insulin secretion in response to Cch as well as P70S6K and ERK1/2 proteins phosphorylation, also suggest the participation of the cholinergic pathway in INGAP-PP mediated effects

ASSUNTO(S)

ratos neonatos gene expression islets of langerhans langerhans expressão genica ingap insulin neonate rats ilhotas de insulina - secreção

ACESSO AO ARTIGO

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