Rapamycin Impairs β-Cell Proliferation In Vivo

E. Zahr, R. D. Molano, A. Pileggi, H. Ichii, S. San Jose, N. Bocca, W. An, J. Gonzalez-Quintana, C. Fraker, C. Ricordi, L. Inverardi

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

During pregnancy a high rate of β-cell proliferation occurs, making of this a useful model for the study of islet cell expansion in vivo. We used the murine pregnancy model to assess the effect of Rapamycin treatment on islet cell proliferation in vivo. Rapamycin is routinely used for the prevention of graft rejection in transplanted patients, including islet transplant recipients. As expected, pregnancy led to increased β-cell proliferation, islet yield and skewing in size distribution after isolation and pancreatic insulin content, when compared to non-pregnant females. Rapamycin treatment resulted in reduced beta cell proliferation in pregnant mice, while minimal effects of Rapamycin treatment were observed on islet function both in vivo and in vitro. Rapamycin treatment of islets resulted in reduced phosphorylation of p70s6k, a downstream effector molecule of mTOR and increased ERK1/2 phosphorylation. In conclusion, β-cell replication is reduced under Rapamycin treatment in vivo, suggesting that this mechanism may be operational and impair β-cell renewal in transplanted patients.

Original languageEnglish (US)
Pages (from-to)436-437
Number of pages2
JournalTransplantation proceedings
Volume40
Issue number2
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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    Zahr, E., Molano, R. D., Pileggi, A., Ichii, H., San Jose, S., Bocca, N., An, W., Gonzalez-Quintana, J., Fraker, C., Ricordi, C., & Inverardi, L. (2008). Rapamycin Impairs β-Cell Proliferation In Vivo. Transplantation proceedings, 40(2), 436-437. https://doi.org/10.1016/j.transproceed.2008.02.011