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
Open accessAbstract
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, p70 S6K 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 p70 S6K 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 p70 S6K 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 p70 S6K ) 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.
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Activation of STAT5, MAPK, phosphatidylinositol 3-kinase and IRS1/2 enhances β-cell compensation downstream of the prolactin receptor in vitro.
“Although activation of multiple signaling pathways such as STAT5, MAPK and phosphatidylinositol 3-kinase and IRS1/2 enhances β-cell compensation downstream of the prolactin receptor in vitro [52–54], it is not clear whether PRL and/or PL stimulate these pathways in vivo.”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [53]
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- Authors
- Amaral, M. E. C., Cunha, D. A., Anhê, G. F., Ueno, M., Carneiro, E. M., Velloso, L. A., Bordin, S., & Boschero, A. C.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade de São Paulo (BR)
- Corresponding author
- Boschero, Antonio C
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2004-12
- Volume
- 183
- Issue
- 3
- Pages
- 469-476
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2148583270
- Cited by
- 110
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 6 · 2012: 8
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- prolactin, prolactin receptor, pancreatic islets, islet mass, glucose sensitivity, PI3K signaling, MAPK signaling, ERK1/2, Akt, p70S6K, Shc, insulin receptor substrate, insulin secretion, pregnancy, antisense oligonucleotides
- MeSH terms
- Insulin Secretion, Animals, Cells, Cultured, Female, Glucose, Insulin, Islets of Langerhans, Phosphorylation, Pregnancy, Proto-Oncogene Proteins, Receptors, Prolactin, Oligonucleotides, Antisense, Rats, Wistar, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, Ribosomal Protein S6 Kinases, 70-kDa, Proto-Oncogene Proteins c-akt, Rats
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