Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway

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 a...

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Autores principales: Barbosa, Helena C., Bordin, Silvana, Anhê, Gabriel, Persaud, Shanta J., Bowe, James, Borelli, María Inés, Gagliardino, Juan José, Boschero, Antonio C.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2008
Materias:
Ciencias Médicas
Islet neogenesis associated protein
insulin secretion
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84230
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84230
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Islet neogenesis associated protein
insulin secretion
spellingShingle Ciencias Médicas
Islet neogenesis associated protein
insulin secretion
Barbosa, Helena C.
Bordin, Silvana
Anhê, Gabriel
Persaud, Shanta J.
Bowe, James
Borelli, María Inés
Gagliardino, Juan José
Boschero, Antonio C.
Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
topic_facet Ciencias Médicas
Islet neogenesis associated protein
insulin secretion
description 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 P13K, 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<SUP>-Ser473</SUP> and MAPK3/1<SUP>-Thr202/ Tyr204</SUP> 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 <i>Akt1</i>, <i>Frap1</i>, and <i>Mapk1</i> mRNAs as well as of the muscarinic M3 receptor subtype, and phospholipase C (PLC)-β2 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<SUP>-Thr389</SUP> 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 P13K and MAPK signaling pathways. The observations of INGAPP-PP-stimulated up-regulation of cholinergic M3 receptors and PLC- proteins, enhanced P70S6K and MAPK3/1 phosphorylation and Cch-induced insulin secretion suggest a participation of the cholinergic pathway in INGAP-PP-mediated effects.
format Articulo
Articulo
author Barbosa, Helena C.
Bordin, Silvana
Anhê, Gabriel
Persaud, Shanta J.
Bowe, James
Borelli, María Inés
Gagliardino, Juan José
Boschero, Antonio C.
author_facet Barbosa, Helena C.
Bordin, Silvana
Anhê, Gabriel
Persaud, Shanta J.
Bowe, James
Borelli, María Inés
Gagliardino, Juan José
Boschero, Antonio C.
author_sort Barbosa, Helena C.
title Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
title_short Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
title_full Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
title_fullStr Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
title_full_unstemmed Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway
title_sort islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway
publishDate 2008
url http://sedici.unlp.edu.ar/handle/10915/84230
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