| First Author | Ou K | Year | 2018 |
| Journal | Mol Metab | Volume | 11 |
| Pages | 212-217 | PubMed ID | 29650351 |
| Mgi Jnum | J:301849 | Mgi Id | MGI:6507256 |
| Doi | 10.1016/j.molmet.2018.03.009 | Citation | Ou K, et al. (2018) Overexpression of ST5, an activator of Ras, has no effect on beta-cell proliferation in adult mice. Mol Metab 11:212-217 |
| abstractText | OBJECTIVE: Both Type I and Type II diabetes mellitus result from insufficient functional beta-cell mass. Efforts to increase beta-cell proliferation as a means to restore beta-cell mass have been met with limited success. Suppression of Tumorigenicity 5 (ST5) activates Ras/Erk signaling in the presence of Epidermal Growth Factor (EGF). In the pancreatic islet, Ras/Erk signaling is required for augmented beta-cell proliferation during pregnancy, suggesting that ST5 is an appealing candidate to enhance adult beta-cell proliferation. We aimed to test the hypothesis that overexpression of ST5 drives adult beta-cell proliferation. METHODS: We utilized a doxycycline-inducible bitransgenic mouse model to activate beta-cell-specific expression of human ST5 in adult mice at will. Islet morphology, beta-cell proliferation, and beta-cell mass in control and ST5-overexpressing (ST5 OE) animals were analyzed by immunofluorescent staining, under basal and two stimulated metabolic states: pregnancy and streptozotocin (STZ)-induced beta-cell loss. RESULTS: Doxycycline treatment resulted in robust ST5 overexpression in islets from 12-16 week-old ST5 OE animals compared to controls, without affecting the islet morphology and identity of the beta-cells. Under both basal and metabolically stimulated pregnancy states, beta-cell proliferation and mass were comparable in ST5 OE and control animals. Furthermore, there was no detectable difference in beta-cell proliferation between ST5 OE and control animals in response to STZ-induced beta-cell loss. CONCLUSIONS: We successfully derived an inducible bitransgenic mouse model to overexpress ST5 specifically in beta-cells. However, our findings demonstrate that ST5 overexpression by itself has no mitogenic effect on the adult beta-cell under basal and metabolically challenged states. |
