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Mehta, Zenobia B.; Johnston, Natalie R.; Nguyen-Tu, Marie-Sophie; Broichhagen, Johannes; Schultz, Peter; Larner, Dean P.; Leclerc, Isabelle; Trauner, Dirk; Rutter, Guy A.; Hodson, David J. (2017): Remote control of glucose homeostasis in vivo using photopharmacology. In: Scientific Reports, Vol. 7, 291
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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.