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Type: Artigo de periódico
Title: Islet Neogenesis-associated Protein Signaling In Neonatal Pancreatic Rat Islets: Involvement Of The Cholinergic Pathway.
Author: Barbosa, Helena C
Bordin, Silvana
Anhê, Gabriel
Persaud, Shanta J
Bowe, James
Borelli, Maria I
Gagliardino, Juan J
Boschero, Antonio C
Abstract: Islet neogenesis associated protein (INGAP) increases islet mass and insulin secretion in neonatal and adult rat islets. In the present study, we measured the short- and long-term effects of INGAP-PP (a pentadecapeptide having the 104-118 amino acid sequence of INGAP) upon islet protein expression and phosphorylation of components of the PI3K, MAPK and cholinergic pathways, and on insulin secretion. Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1(-Ser473) and MAPK3/1(-Thr202/Tyr204) phosphorylation and INGAP-PP also acutely increased insulin secretion from islets perifused with 2 and 20 mM glucose. Islets cultured for 4 days in the presence of INGAP-PP showed an increased expression of Akt1, Frap1, and Mapk1 mRNAs as well as of the muscarinic M3 receptor subtype, and phospholipase C (PLC)-beta2 proteins. These islets also showed increased Akt1 and MAPK3/1 protein phosphorylation. Brief exposure of INGAP-PP-treated islets to carbachol (Cch) significantly increased P70S6K(-Thr389) and MAPK3/1 phosphorylation and these islets released more insulin when challenged with Cch that was prevented by the M3 receptor antagonist 4-DAMP, in a concentration-dependent manner. In conclusion, these data indicate that short- and long-term exposure to INGAP-PP significantly affects the expression and the phosphorylation of proteins involved in islet PI3K and MAPK signaling pathways. The observations of INGAPP-PP-stimulated up-regulation of cholinergic M3 receptors and PLC-beta2 proteins, enhanced P70S6K and MAPK3/1 phosphorylation and Cch-induced insulin secretion suggest a participation of the cholinergic pathway in INGAP-PP-mediated effects.
Subject: Animals
Animals, Newborn
Antigens, Neoplasm
Carrier Proteins
In Vitro Techniques
Islets Of Langerhans
Lectins, C-type
Mitogen-activated Protein Kinase 1
Mitogen-activated Protein Kinase 3
Phosphotransferases (alcohol Group Acceptor)
Proto-oncogene Proteins C-akt
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases, 70-kda
Signal Transduction
Tor Serine-threonine Kinases
Tumor Markers, Biological
Citation: The Journal Of Endocrinology. v. 199, n. 2, p. 299-306, 2008-Nov.
Rights: fechado
Identifier DOI: 10.1677/JOE-08-0309
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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