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Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome

Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo m...

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Autores principales: King, Aileen J. F., Griffiths, Lisa A., Persaud, Shanta J., Jones, Peter M., Howell, Simon L., Welsh, Nils
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900069/
https://www.ncbi.nlm.nih.gov/pubmed/26953716
http://dx.doi.org/10.3109/03009734.2016.1151090
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author King, Aileen J. F.
Griffiths, Lisa A.
Persaud, Shanta J.
Jones, Peter M.
Howell, Simon L.
Welsh, Nils
author_facet King, Aileen J. F.
Griffiths, Lisa A.
Persaud, Shanta J.
Jones, Peter M.
Howell, Simon L.
Welsh, Nils
author_sort King, Aileen J. F.
collection PubMed
description Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.
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spelling pubmed-49000692016-06-22 Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome King, Aileen J. F. Griffiths, Lisa A. Persaud, Shanta J. Jones, Peter M. Howell, Simon L. Welsh, Nils Ups J Med Sci Research Articles Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome. Taylor & Francis 2016-05 2016-03-07 /pmc/articles/PMC4900069/ /pubmed/26953716 http://dx.doi.org/10.3109/03009734.2016.1151090 Text en © 2016 The Author(s). Published by Taylor & Francis. http://creativecommons.org/Licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
King, Aileen J. F.
Griffiths, Lisa A.
Persaud, Shanta J.
Jones, Peter M.
Howell, Simon L.
Welsh, Nils
Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title_full Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title_fullStr Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title_full_unstemmed Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title_short Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
title_sort imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900069/
https://www.ncbi.nlm.nih.gov/pubmed/26953716
http://dx.doi.org/10.3109/03009734.2016.1151090
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