Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782233196546490368 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3354320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yangshibing rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT leehyeyoung rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT youngdavidmatthew rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT tienanchi rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT rowsonbaldwinashley rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT shuyuyu rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT janyuhnung rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity AT janlilyyeh rapamycininducesglucoseintoleranceinmicebyreducingisletmassinsulincontentandinsulinsensitivity |