Remote control of glucose homeostasis in vivo using photopharmacology

Research output: Contribution to journalArticle

Authors

  • Zenobia Mehta
  • Natalie Johnston
  • Marie-Sophie Nguyen-Tu
  • Johannes Broichhagen
  • Peter G Schultz
  • Isabelle Leclerc
  • Dirk Trauner
  • Guy Rutter

Colleges, School and Institutes

External organisations

  • Imperial College London
  • Department of Chemistry, Ludwig-Maximilians-Universitat Muchen, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Muchen, Germany

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.

Details

Original languageEnglish
Article number291
JournalScientific Reports
Volume7
Publication statusPublished - 22 Mar 2017

Keywords

  • Potassium channels, Type 2 diabetes