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Optical control of insulin release using a photoswitchable sulfonylurea

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  • Johannes Broichhagen

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München, Germany)

  • Matthias Schönberger

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München, Germany)

  • Simon C. Cork

    (Physiology and Pharmacology, University College London)

  • James A. Frank

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München, Germany)

  • Piero Marchetti

    (Islet Cell Laboratory, University of Pisa)

  • Marco Bugliani

    (Islet Cell Laboratory, University of Pisa)

  • A. M. James Shapiro

    (Clinical Islet Laboratory and Clinical Islet transplant program, University of Alberta)

  • Stefan Trapp

    (Physiology and Pharmacology, University College London)

  • Guy A. Rutter

    (Section of Cell Biology, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, Du Cane Road)

  • David J. Hodson

    (Section of Cell Biology, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, Du Cane Road)

  • Dirk Trauner

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München, Germany)

Abstract

Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM.

Suggested Citation

  • Johannes Broichhagen & Matthias Schönberger & Simon C. Cork & James A. Frank & Piero Marchetti & Marco Bugliani & A. M. James Shapiro & Stefan Trapp & Guy A. Rutter & David J. Hodson & Dirk Trauner, 2014. "Optical control of insulin release using a photoswitchable sulfonylurea," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6116
    DOI: 10.1038/ncomms6116
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