| First Author | Cebrian A | Year | 2002 |
| Journal | Diabetes | Volume | 51 |
| Issue | 10 | Pages | 3003-13 |
| PubMed ID | 12351440 | Mgi Jnum | J:79220 |
| Mgi Id | MGI:2387521 | Doi | 10.2337/diabetes.51.10.3003 |
| Citation | Cebrian A, et al. (2002) Overexpression of Parathyroid Hormone-Related Protein Inhibits Pancreatic beta-Cell Death In Vivo and In Vitro. Diabetes 51(10):3003-13 |
| abstractText | Pancreatic beta-cell survival is critical in the setting of diabetes as well as in islet transplantation. Transgenic mice overexpressing parathyroid hormone-related protein (PTHrP) targeted to beta-cells using the rat insulin II promoter (RIP) display hyperinsulinemia, hypoglycemia, and islet hyperplasia, without a concomitant increase in beta-cell proliferation rate or enlargement of individual beta-cell size. Thus, the mechanism for increased beta-cell mass is unknown. In this study, we demonstrated that beta-cells of transgenic mice are resistant to the cytotoxic effects of streptozotocin (STZ) in vivo, as documented by a sixfold reduction in the rate of STZ-induced beta-cell death in RIP-PTHrP mice relative to their normal siblings. The reduced cell death in transgenic mice is due neither to their increased islet mass nor to a decrease in their sensing of STZ, but rather results from PTHrP-induced resistance to beta-cell death. This is also demonstrated in vitro by markedly reduced cell death rates observed in beta-cells of transgenic mice compared with normal mice when cultured in the absence of serum and glucose or in the presence of STZ. Finally, we demonstrated that NH(2)-terminal PTHrP inhibits beta-cell death. These findings support the concept that PTHrP overexpression increases islet mass in transgenic mice through inhibition of beta-cell death. |
