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Remote control of glucose homeostasis in vivo using photopharmacology

Zenobia B Mehta1, Natalie R Johnston1, Marie-Sophie Nguyen-Tu1

  • 1Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, London, W12 0NN, UK.

Scientific Reports
|March 24, 2017
PubMed

Insights

Photopharmacology uses light to control drug activity, improving specificity. A new drug, JB253, shows promise for optically controlling glucose in mice, suggesting future diabetes treatments.

Area of Science:

  • Pharmacology
  • Biomedical Engineering
  • Endocrinology

Background:

  • Photopharmacology offers precise spatiotemporal control of drug activity.
  • This approach aims to enhance drug specificity and minimize off-target effects.
  • Current treatments for metabolic diseases lack precise control mechanisms.

Purpose of the Study:

  • To assess the toxicology and in vivo efficacy of the photoswitchable sulfonylurea JB253.
  • To demonstrate the potential of photopharmacology in managing metabolic homeostasis.
  • To evaluate JB253 as a potential therapeutic agent for type 2 diabetes.

Main Methods:

  • Comprehensive toxicology assessment of JB253, including mutagenicity and dose-ranging studies.
  • In vivo testing in rodent models to evaluate drug tolerability and efficacy.
  • Optical control of glucose homeostasis using blue light delivered to the pancreas.

Main Results:

  • JB253 demonstrated good tolerability with minimal mutagenicity in toxicology studies.
  • Blue light delivery to the pancreas successfully controlled glucose homeostasis in anesthetized mice.
  • The photoswitchable drug JB253 showed efficacy in an in vivo model.

Conclusions:

  • JB253 is a well-tolerated photoswitchable compound with potential for therapeutic applications.
  • Photopharmacology using JB253 offers a novel strategy for optically controlling glucose homeostasis.
  • These findings support the potential application of photopharmacology in treating type 2 diabetes and other metabolic disorders.

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