Remote control of glucose homeostasis in vivo using photopharmacology

Abstract Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to compreh...

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Autores principales:	Zenobia B. Mehta, Natalie R. Johnston, Marie-Sophie Nguyen-Tu, Johannes Broichhagen, Peter Schultz, Dean P. Larner, Isabelle Leclerc, Dirk Trauner, Guy A. Rutter, David J. Hodson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ef948b53454487d84dd10b347df1987
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spelling	oai:doaj.org-article:3ef948b53454487d84dd10b347df19872021-12-02T11:41:01ZRemote control of glucose homeostasis in vivo using photopharmacology10.1038/s41598-017-00397-02045-2322https://doaj.org/article/3ef948b53454487d84dd10b347df19872017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00397-0https://doaj.org/toc/2045-2322Abstract Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas. These studies provide the first demonstration that photopharmacology may one day be applicable to the light-guided treatment of type 2 diabetes and other metabolic disease states in vivo in humans.Zenobia B. MehtaNatalie R. JohnstonMarie-Sophie Nguyen-TuJohannes BroichhagenPeter SchultzDean P. LarnerIsabelle LeclercDirk TraunerGuy A. RutterDavid J. HodsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zenobia B. Mehta Natalie R. Johnston Marie-Sophie Nguyen-Tu Johannes Broichhagen Peter Schultz Dean P. Larner Isabelle Leclerc Dirk Trauner Guy A. Rutter David J. Hodson Remote control of glucose homeostasis in vivo using photopharmacology
description	Abstract Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas. These studies provide the first demonstration that photopharmacology may one day be applicable to the light-guided treatment of type 2 diabetes and other metabolic disease states in vivo in humans.
format	article
author	Zenobia B. Mehta Natalie R. Johnston Marie-Sophie Nguyen-Tu Johannes Broichhagen Peter Schultz Dean P. Larner Isabelle Leclerc Dirk Trauner Guy A. Rutter David J. Hodson
author_facet	Zenobia B. Mehta Natalie R. Johnston Marie-Sophie Nguyen-Tu Johannes Broichhagen Peter Schultz Dean P. Larner Isabelle Leclerc Dirk Trauner Guy A. Rutter David J. Hodson
author_sort	Zenobia B. Mehta
title	Remote control of glucose homeostasis in vivo using photopharmacology
title_short	Remote control of glucose homeostasis in vivo using photopharmacology
title_full	Remote control of glucose homeostasis in vivo using photopharmacology
title_fullStr	Remote control of glucose homeostasis in vivo using photopharmacology
title_full_unstemmed	Remote control of glucose homeostasis in vivo using photopharmacology
title_sort	remote control of glucose homeostasis in vivo using photopharmacology
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3ef948b53454487d84dd10b347df1987
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Remote control of glucose homeostasis in vivo using photopharmacology

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