Rapamycin Impairs β-Cell Proliferation In Vivo

E. Zahr, Ruth Molano, A. Pileggi, H. Ichii, S. San Jose, N. Bocca, W. An, J. Gonzalez-Quintana, Christopher Fraker, Camillo Ricordi, Luca A Inverardi

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

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Sirolimus
Cell Proliferation
Islets of Langerhans
Pregnancy
Phosphorylation
70-kDa Ribosomal Protein S6 Kinases
Therapeutics
Graft Rejection
Insulin

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Zahr, E., Molano, R., Pileggi, A., Ichii, H., San Jose, S., Bocca, N., ... Inverardi, L. A. (2008). Rapamycin Impairs β-Cell Proliferation In Vivo. Transplantation Proceedings, 40(2), 436-437. https://doi.org/10.1016/j.transproceed.2008.02.011

Rapamycin Impairs β-Cell Proliferation In Vivo. / Zahr, E.; Molano, Ruth; Pileggi, A.; Ichii, H.; San Jose, S.; Bocca, N.; An, W.; Gonzalez-Quintana, J.; Fraker, Christopher; Ricordi, Camillo; Inverardi, Luca A.

In: Transplantation Proceedings, Vol. 40, No. 2, 01.03.2008, p. 436-437.

Research output: Contribution to journalArticle

Zahr, E, Molano, R, Pileggi, A, Ichii, H, San Jose, S, Bocca, N, An, W, Gonzalez-Quintana, J, Fraker, C, Ricordi, C & Inverardi, LA 2008, 'Rapamycin Impairs β-Cell Proliferation In Vivo', Transplantation Proceedings, vol. 40, no. 2, pp. 436-437. https://doi.org/10.1016/j.transproceed.2008.02.011
Zahr E, Molano R, Pileggi A, Ichii H, San Jose S, Bocca N et al. Rapamycin Impairs β-Cell Proliferation In Vivo. Transplantation Proceedings. 2008 Mar 1;40(2):436-437. https://doi.org/10.1016/j.transproceed.2008.02.011
Zahr, E. ; Molano, Ruth ; Pileggi, A. ; Ichii, H. ; San Jose, S. ; Bocca, N. ; An, W. ; Gonzalez-Quintana, J. ; Fraker, Christopher ; Ricordi, Camillo ; Inverardi, Luca A. / Rapamycin Impairs β-Cell Proliferation In Vivo. In: Transplantation Proceedings. 2008 ; Vol. 40, No. 2. pp. 436-437.
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