@article{51bbb15e334a42dd8ef23327777c714f,
title = "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 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.",
author = "Mehta, {Zenobia B.} and Johnston, {Natalie R.} and Nguyen-Tu, {Marie Sophie} and Johannes Broichhagen and Peter Schultz and Larner, {Dean P.} and Isabelle Leclerc and Dirk Trauner and Rutter, {Guy A.} and Hodson, {David J.}",
note = "Funding Information: We thank V. Fisher for her help with ethical review of the animal studies and Mariia Palchyk for excellent synthetic assistance. We are grateful to Pierre Fontanaud (Institut de G{\'e}nomique Fonctionnelle, Montpellier, France) for expert statistical advice. N.R.J. was supported by a Diabetes UK RW and JM Collins Studentship (12/0004601). J.B. was supported by a European Foundation for the Study of Diabetes (EFSD) Albert Renold Young Scientist Fellowship and a Studienstiftung des deutschen Volkes PhD Studentship. G.A.R. was supported by Wellcome Trust Senior Investigator (WT098424AIA) and Royal Society Wolfson Research Merit Awards, and by MRC Programme (MR/J0003042/1), Biological and Biotechnology Research Council (BB/J015873/1) and Diabetes UK Project (11/0004210) Grants. D.J.H. was supported by Diabetes UK R.D. Lawrence (12/0004431), EFSD/Novo Nordisk Rising Star and Birmingham Fellowships, and a Wellcome Trust Institutional Support Award. D.J.H and G.A.R. were supported by Imperial Confidence in Concept (ICiC) and MRC Project (MR/ N00275X/1) Grants. This project has received funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (Starting Grant 715884 to D.J.H. and Advanced Grant 268795 to D.T.).",
year = "2017",
doi = "10.1038/s41598-017-00397-0",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}