Rapamycin Induces Autophagy in Islets: Relevance in Islet Transplantation

M. Tanemura, A. Saga, K. Kawamoto, T. Machida, T. Deguchi, T. Nishida, Y. Sawa, Y. Doki, M. Mori, T. Ito

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Islet transplantation can provide insulin independence in patients with type 1 diabetes mellitus. However, islet allograft recipients exhibit a gradual decline in insulin independence, and only 10% do not require insulin at 5 years. This decline may reflect drug toxicity to islet β cells. Rapamycin, a central immunosuppressant in islet transplantation, is a mammalian target of rampamycin inhibitor that induces autophagy. The relative contributions of autophagy in transplanted islets are poorly understood. Therefore, in the present study we sought to evaluate the effects of rapamycin on islet β cells. Rapamycin treatment of islets resulted in accumulation of membrane-bound light chain 3 (LC3-II) protein, an early marker of autophagy. In addition, rapamycin treatment of isolated islets elicited not only reduction of viability but also downregulation of in vitro potency. To further examine the occurrence of autophagy in rapamycin-treated islets, we used GFP (green fluorescent protein)-LC3 transgenic mice that express a fluorescent autophagosome marker. The GFP-LC3 signals were markedly increased in rapamycin treated islets compared with control islets. In addition, to show improvement by blockade of autophagic signaling, islets were treated with rapamycin in the presence of 3-methyladenine, which inhibits autophagy. Thereafter, both islet viability and islet potency were dramatically improved. The number of GFP-LC3 dots clearly increased after 3-MA treatment. Thus, rapamycin treatment of islets induces autophagy in vitro. This phenomenon may contribute to the progressive graft dysfunction of transplanted islets. Therapeutically targeting this novel signaling may yield significant benefits for long-term islet survival.

Original languageEnglish
Pages (from-to)334-338
Number of pages5
JournalTransplantation Proceedings
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

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Islets of Langerhans Transplantation
Autophagy
Sirolimus
Green Fluorescent Proteins
Insulin
Islets of Langerhans
Therapeutics
Immunosuppressive Agents
Drug-Related Side Effects and Adverse Reactions
Type 1 Diabetes Mellitus
Transgenic Mice
Allografts
Down-Regulation
Transplants
Light
Membranes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

Tanemura, M., Saga, A., Kawamoto, K., Machida, T., Deguchi, T., Nishida, T., ... Ito, T. (2009). Rapamycin Induces Autophagy in Islets: Relevance in Islet Transplantation. Transplantation Proceedings, 41(1), 334-338. https://doi.org/10.1016/j.transproceed.2008.10.032

Rapamycin Induces Autophagy in Islets : Relevance in Islet Transplantation. / Tanemura, M.; Saga, A.; Kawamoto, K.; Machida, T.; Deguchi, T.; Nishida, T.; Sawa, Y.; Doki, Y.; Mori, M.; Ito, T.

In: Transplantation Proceedings, Vol. 41, No. 1, 01.01.2009, p. 334-338.

Research output: Contribution to journalArticle

Tanemura, M, Saga, A, Kawamoto, K, Machida, T, Deguchi, T, Nishida, T, Sawa, Y, Doki, Y, Mori, M & Ito, T 2009, 'Rapamycin Induces Autophagy in Islets: Relevance in Islet Transplantation', Transplantation Proceedings, vol. 41, no. 1, pp. 334-338. https://doi.org/10.1016/j.transproceed.2008.10.032
Tanemura M, Saga A, Kawamoto K, Machida T, Deguchi T, Nishida T et al. Rapamycin Induces Autophagy in Islets: Relevance in Islet Transplantation. Transplantation Proceedings. 2009 Jan 1;41(1):334-338. https://doi.org/10.1016/j.transproceed.2008.10.032
Tanemura, M. ; Saga, A. ; Kawamoto, K. ; Machida, T. ; Deguchi, T. ; Nishida, T. ; Sawa, Y. ; Doki, Y. ; Mori, M. ; Ito, T. / Rapamycin Induces Autophagy in Islets : Relevance in Islet Transplantation. In: Transplantation Proceedings. 2009 ; Vol. 41, No. 1. pp. 334-338.
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