Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/196050
Type: Artigo de periódico
Title: Participation Of Prolactin Receptors And Phosphatidylinositol 3-kinase And Map Kinase Pathways In The Increase In Pancreatic Islet Mass And Sensitivity To Glucose During Pregnancy.
Author: Amaral, Maria E C
Cunha, Daniel A
Anhê, Gabriel F
Ueno, Mirian
Carneiro, Everardo M
Velloso, Lício A
Bordin, Silvana
Boschero, Antonio C
Abstract: Prolactin (PRL) exerts its biological effects mainly by activating the Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling pathway. We have recently demonstrated that PRL also stimulates the insulin receptor substrates/phosphatidylinositol 3-kinase (IRSs/PI3K) and SH2-plekstrin homology domain (SHC)/ERK pathways in islets of neonatal rats. In the present study, we investigated the involvement of the PI3K and MAP kinase (MAPK) cascades in islet development and growth in pregnant rats. The protein expression of AKT1, p70S6K and SHC was higher in islets from pregnant compared with control rats. Higher basal levels of tyrosine phosphorylation were found in classic transducers of insulin cell signaling (IRS1, IRS2 and SHC). Increased levels of threonine/tyrosine phosphorylation of ERK1/2 and serine phosphorylation of AKT and p70S6K were also detected. To assess the participation of PRL in these phenomena, pregnant and control rats were treated with an antisense oligonucleotide to reduce the expression of the PRL receptor (PRLR). Phosphorylation of AKT was reduced in islets from pregnant and control rats, whereas p70S6K protein levels were reduced only in islets from treated pregnant rats. Finally, glucose-induced insulin secretion was reduced in islets from pregnant but not from control rats treated with the PRLR antisense oligonucleotide. In conclusion, downstream proteins of the PI3K (AKT and p70S6K) and MAPK (SHC and ERK1/2) cascades are regulated by PRL signaling in islets from pregnant rats. These findings indicate that these pathways participate in the increase in islet mass and the sensitivity to glucose during pregnancy.
Subject: Animals
Cells, Cultured
Female
Glucose
Insulin
Islets Of Langerhans
Map Kinase Signaling System
Oligonucleotides, Antisense
Phosphatidylinositol 3-kinases
Phosphorylation
Pregnancy
Protein-serine-threonine Kinases
Proto-oncogene Proteins
Proto-oncogene Proteins C-akt
Rats
Rats, Wistar
Receptors, Prolactin
Ribosomal Protein S6 Kinases, 70-kda
Rights: fechado
Identifier DOI: 10.1677/joe.1.05547
Address: http://www.ncbi.nlm.nih.gov/pubmed/15590973
Date Issue: 2004
Appears in Collections:Unicamp - Artigos e Outros Documentos

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