Optical control of insulin release using a photoswitchable sulfonylurea

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5116
JournalNature Communications
Volume5
DOIs
StatePublished - Oct 14 2014

Fingerprint

diabetes mellitus
KATP Channels
insulin
optical control
hypoglycemia
Insulin
Medical problems
homeostasis
rodents
hormones
adenosine triphosphate
interrogation
Insulin-Secreting Cells
acceleration (physics)
cells
glucose
Type 2 Diabetes Mellitus
health
Photosensitivity
Viola

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Broichhagen, J., Schönberger, M., Cork, S. C., Frank, J. A., Marchetti, P., Bugliani, M., ... Trauner, D. (2014). Optical control of insulin release using a photoswitchable sulfonylurea. Nature Communications, 5, [5116]. https://doi.org/10.1038/ncomms6116

Optical control of insulin release using a photoswitchable sulfonylurea. / Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C.; Frank, James A.; Marchetti, Piero; Bugliani, Marco; Shapiro, A. M James; Trapp, Stefan; Rutter, Guy A.; Hodson, David J.; Trauner, Dirk.

In: Nature Communications, Vol. 5, 5116, 14.10.2014.

Research output: Contribution to journalArticle

Broichhagen, J, Schönberger, M, Cork, SC, Frank, JA, Marchetti, P, Bugliani, M, Shapiro, AMJ, Trapp, S, Rutter, GA, Hodson, DJ & Trauner, D 2014, 'Optical control of insulin release using a photoswitchable sulfonylurea', Nature Communications, vol. 5, 5116. https://doi.org/10.1038/ncomms6116
Broichhagen J, Schönberger M, Cork SC, Frank JA, Marchetti P, Bugliani M et al. Optical control of insulin release using a photoswitchable sulfonylurea. Nature Communications. 2014 Oct 14;5. 5116. https://doi.org/10.1038/ncomms6116
Broichhagen, Johannes ; Schönberger, Matthias ; Cork, Simon C. ; Frank, James A. ; Marchetti, Piero ; Bugliani, Marco ; Shapiro, A. M James ; Trapp, Stefan ; Rutter, Guy A. ; Hodson, David J. ; Trauner, Dirk. / Optical control of insulin release using a photoswitchable sulfonylurea. In: Nature Communications. 2014 ; Vol. 5.
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