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

doi:10.1038/ncomms6116

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

Medical and Dental Sciences

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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 language	English
Article number	5116
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6116
Publication status	Published - 14 Oct 2014

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Open Access funded by Wellcome Trust
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Cite this

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title = "Optical control of insulin release using a photoswitchable sulfonylurea",

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.",

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AU - Broichhagen, Johannes

AU - Schönberger, Matthias

AU - Cork, Simon C

AU - Frank, James A

AU - Marchetti, Piero

AU - Bugliani, Marco

AU - Shapiro, A M James

AU - Trapp, Stefan

AU - Rutter, Guy A

AU - Hodson, David J

AU - Trauner, Dirk

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N2 - 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.

AB - 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.

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Optical control of insulin release using a photoswitchable sulfonylurea

Abstract

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