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Optical control of insulin release using a photoswitchable sulfonylurea

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Title: Optical control of insulin release using a photoswitchable sulfonylurea
Authors: Rutter, GA
Broichhagen, J
Schönberger, M
Cork, SC
Frank, JA
Marchetti, P
Bugliani, M
Shapiro, AMJ
Trapp, S
Hodson, DJ
Trauner, D
Item Type: Journal Article
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.
Issue Date: 14-Oct-2014
Date of Acceptance: 1-Sep-2014
URI: http://hdl.handle.net/10044/1/17857
DOI: 10.1038/ncomms6116
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 5
Issue: 10
Copyright Statement: © The Authors.This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Diabetes UK
Diabetes UK
Medical Research Council (MRC)
Funder's Grant Number: 15821
12/0004529
MR/K001981/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GLYCEMIC CONTROL
BETA-CELLS
SECRETION
CHANNELS
THERAPIES
HYPERGLYCEMIA
STIMULATION
TOLBUTAMIDE
HOMEOSTASIS
MANAGEMENT
Animals
Biological Transport
Cell Line
Female
Humans
Hypoglycemic Agents
Insulin
Insulin Secretion
Insulin-Secreting Cells
Islets of Langerhans
KATP Channels
Light
Male
Mice
Mice, Inbred C57BL
Sulfonylurea Compounds
Islets of Langerhans
Cell Line
Animals
Mice, Inbred C57BL
Humans
Mice
Sulfonylurea Compounds
Insulin
Hypoglycemic Agents
Biological Transport
Light
Female
Male
Insulin-Secreting Cells
KATP Channels
Insulin Secretion
Publication Status: Published
Article Number: ARTN 5116
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons