Remote control of glucose homeostasis in vivo using photopharmacology

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number291
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • General

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