| Participation of Akt, menin, and p21 in pregnancy-induced beta-cell proliferation. | |
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MedLine Citation:
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PMID: 21239436 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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β-Cell mass increases during pregnancy to accommodate for insulin resistance. This increase is mainly due to β-cell proliferation, a process that requires intact prolactin receptor (Prlr) signaling. Signaling molecules that are known to regulate β-cell proliferation include Jak2, Akt, the tumor suppressor menin, and cell cycle proteins. Whether these pathways are involved in prolactin-mediated β-cell proliferation is unknown. Using the heterozygous prolactin receptor-null (Prlr(+/-)) mice, we isolated pancreatic islets from both Prlr(+/+) and Prlr(+/-) mice on d 0 and 15 of pregnancy and examined the expression levels of these signaling molecules. In the wild-type mice (Prlr(+/+)), both phospho-Jak2 and phospho-Akt expression in pancreatic islets increased during pregnancy, which were attenuated in the pregnant Prlr(+/-) mice. During pregnancy, menin expression was reduced by 50 and 20% in the Prlr(+/+) and the Prlr(+/-) mice, respectively, and the pregnant Prlr(+/-) mice had higher islet p18 levels than the Prlr(+/+) mice. Interestingly, between d 0 and 15 of pregnancy, expression of cyclin inhibitory protein p21(cip) was increased in the Prlr(+/+) mice, but this increase was blunted in the Prlr(+/-) mice. Lastly, we did not find any difference in the expression levels of cyclins D1, D2, and inhibitory kinases between the pregnant Prlr(+/+) and Prlr(+/-) mice. Therefore, we conclude that during pregnancy, placental hormones act through the prolactin receptor to increase β-cell mass by up regulating β-cell proliferation by engaging Jak2, Akt, menin/p18, and p21. Future studies will determine the relative contribution of these molecules in maintaining normal glucose homeostasis during pregnancy. |
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Authors:
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Elizabeth Hughes; Carol Huang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-01-14 |
Journal Detail:
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Title: Endocrinology Volume: 152 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-22 Completed Date: 2011-04-27 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 847-55 Citation Subset: AIM; IM |
Affiliation:
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University of Calgary, Faculty of Medicine, Department of Pediatrics, Calgary, Alberta, Canada T2N 4N1. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation Cyclin-Dependent Kinase Inhibitor p21 / genetics, metabolism* Female Gene Expression Regulation / physiology Insulin Receptor Substrate Proteins / genetics, metabolism Insulin-Secreting Cells / cytology, physiology* Janus Kinase 2 / genetics, metabolism Mice Mice, Knockout NM23 Nucleoside Diphosphate Kinases / genetics, metabolism Phosphorylation Pregnancy Prolactin / metabolism Proto-Oncogene Proteins / genetics, metabolism* Proto-Oncogene Proteins c-akt / genetics, metabolism* Receptors, Prolactin / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/Insulin Receptor Substrate Proteins; 0/Irs2 protein, mouse; 0/Men1 protein, mouse; 0/NM23 Nucleoside Diphosphate Kinases; 0/Proto-Oncogene Proteins; 0/Receptors, Prolactin; 9002-62-4/Prolactin; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/Jak2 protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.4.6/Nme2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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