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Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity

Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose h...

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Autores principales: Yang, Shi-Bing, Lee, Hye Young, Young, David Matthew, Tien, An-Chi, Rowson-Baldwin, Ashley, Shu, Yu Yu, Jan, Yuh Nung, Jan, Lily Yeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354320/
https://www.ncbi.nlm.nih.gov/pubmed/22105852
http://dx.doi.org/10.1007/s00109-011-0834-3
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author Yang, Shi-Bing
Lee, Hye Young
Young, David Matthew
Tien, An-Chi
Rowson-Baldwin, Ashley
Shu, Yu Yu
Jan, Yuh Nung
Jan, Lily Yeh
author_facet Yang, Shi-Bing
Lee, Hye Young
Young, David Matthew
Tien, An-Chi
Rowson-Baldwin, Ashley
Shu, Yu Yu
Jan, Yuh Nung
Jan, Lily Yeh
author_sort Yang, Shi-Bing
collection PubMed
description Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent.
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spelling pubmed-33543202012-05-31 Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity Yang, Shi-Bing Lee, Hye Young Young, David Matthew Tien, An-Chi Rowson-Baldwin, Ashley Shu, Yu Yu Jan, Yuh Nung Jan, Lily Yeh J Mol Med (Berl) Original Article Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent. Springer-Verlag 2011-11-22 2012 /pmc/articles/PMC3354320/ /pubmed/22105852 http://dx.doi.org/10.1007/s00109-011-0834-3 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
Yang, Shi-Bing
Lee, Hye Young
Young, David Matthew
Tien, An-Chi
Rowson-Baldwin, Ashley
Shu, Yu Yu
Jan, Yuh Nung
Jan, Lily Yeh
Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title_full Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title_fullStr Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title_full_unstemmed Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title_short Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
title_sort rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354320/
https://www.ncbi.nlm.nih.gov/pubmed/22105852
http://dx.doi.org/10.1007/s00109-011-0834-3
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