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Pregnancy in rodents is associated with a two- to threefold increase in β-cell mass, which is attributable to large increases in β-cell proliferation, complimented by increases in β-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, β-cell mass does not increase as dramatically during pregnancy, and PRL fails to activate proliferation in human islets in vitro. To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human β-cells. Surprisingly, adult human β-cells express little or no PRLR. As expected, restoration of the hPRLR in human β-cells rescued JAK2-STAT5 signaling in response to PRL. However, rescuing hPRLR-STAT5 signaling nevertheless failed to confer proliferative ability on adult human β-cells in response to PRL. Surprisingly, mouse (but not human) Stat5a overexpression led to upregulation of cyclins D1-3 and cdk4, as well as their nuclear translocation, all of which are associated with β-cell cycle entry. Collectively, the findings show that human β-cells fail to proliferate in response to PRL for multiple reasons, one of which is a paucity of functional PRL receptors, and that murine Stat5 overexpression is able to bypass these impediments.
Pubmed ID: 26159175 RIS Download
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Commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)
View all literature mentionsThe goal of the Integrated Islet Distribution Program (IIDP) is to work with the leading islet isolation centers in the U.S. to distribute high quality human islets to the diabetes research community, in order to advance scientific discoveries and translational medicine.
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
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