| First Author | Chen H | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 11 | Pages | 3784-97 |
| PubMed ID | 26159175 | Mgi Jnum | J:246392 |
| Mgi Id | MGI:5922984 | Doi | 10.2337/db15-0083 |
| Citation | Chen H, et al. (2015) Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human beta-Cells. Diabetes 64(11):3784-97 |
| abstractText | Pregnancy in rodents is associated with a two- to threefold increase in beta-cell mass, which is attributable to large increases in beta-cell proliferation, complimented by increases in beta-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, beta-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 beta-cells. Surprisingly, adult human beta-cells express little or no PRLR. As expected, restoration of the hPRLR in human beta-cells rescued JAK2-STAT5 signaling in response to PRL. However, rescuing hPRLR-STAT5 signaling nevertheless failed to confer proliferative ability on adult human beta-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 beta-cell cycle entry. Collectively, the findings show that human beta-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. |
