PMID- 25311795
OWN - NLM
STAT- MEDLINE
DCOM- 20151124
LR  - 20220409
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 5
DP  - 2014 Oct 14
TI  - Optical control of insulin release using a photoswitchable sulfonylurea.
PG  - 5116
LID - 10.1038/ncomms6116 [doi]
LID - 5116
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.
FAU - Broichhagen, Johannes
AU  - Broichhagen J
AD  - Department of Chemistry, Ludwig-Maximilians-Universitat Munchen, and Munich 
      Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Munchen, 
      Germany.
FAU - Schonberger, Matthias
AU  - Schonberger M
AD  - Department of Chemistry, Ludwig-Maximilians-Universitat Munchen, and Munich 
      Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Munchen, 
      Germany.
FAU - Cork, Simon C
AU  - Cork SC
AD  - Division of Biosciences, Department of Neuroscience, Physiology and Pharmacology, 
      University College London, London WC1E 6BT, UK.
FAU - Frank, James A
AU  - Frank JA
AD  - Department of Chemistry, Ludwig-Maximilians-Universitat Munchen, and Munich 
      Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Munchen, 
      Germany.
FAU - Marchetti, Piero
AU  - Marchetti P
AD  - Department of Clinical and Experimental Medicine, Islet Cell Laboratory, 
      University of Pisa, 56126 Pisa, Italy.
FAU - Bugliani, Marco
AU  - Bugliani M
AD  - Department of Clinical and Experimental Medicine, Islet Cell Laboratory, 
      University of Pisa, 56126 Pisa, Italy.
FAU - Shapiro, A M James
AU  - Shapiro AM
AD  - Clinical Islet Laboratory and Clinical Islet transplant program, University of 
      Alberta, Edmonton, Alberta T6G 2C8, Canada.
FAU - Trapp, Stefan
AU  - Trapp S
AD  - Division of Biosciences, Department of Neuroscience, Physiology and Pharmacology, 
      University College London, London WC1E 6BT, UK.
FAU - Rutter, Guy A
AU  - Rutter GA
AD  - Section of Cell Biology, Department of Medicine, Imperial College London, 
      Imperial Centre for Translational and Experimental Medicine, Hammersmith 
      Hospital, Du Cane Road, London W12 0NN, UK.
FAU - Hodson, David J
AU  - Hodson DJ
AD  - Section of Cell Biology, Department of Medicine, Imperial College London, 
      Imperial Centre for Translational and Experimental Medicine, Hammersmith 
      Hospital, Du Cane Road, London W12 0NN, UK.
FAU - Trauner, Dirk
AU  - Trauner D
AD  - Department of Chemistry, Ludwig-Maximilians-Universitat Munchen, and Munich 
      Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 Munchen, 
      Germany.
LA  - eng
GR  - 12/0004529/DUK_/Diabetes UK/United Kingdom
GR  - 12/0004431/DUK_/Diabetes UK/United Kingdom
GR  - MR/K001981/1/MRC_/Medical Research Council/United Kingdom
GR  - 11/0004210/DUK_/Diabetes UK/United Kingdom
GR  - MR/J0003042/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 268795/ERC_/European Research Council/International
GR  - 098424/WT_/Wellcome Trust/United Kingdom
GR  - WT098424AIA/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141014
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (KATP Channels)
RN  - 0 (Sulfonylurea Compounds)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects/radiation effects
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/chemical synthesis/*pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/drug effects/*metabolism/radiation effects
MH  - Islets of Langerhans/drug effects/metabolism/radiation effects
MH  - KATP Channels/metabolism
MH  - Light
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Sulfonylurea Compounds/chemical synthesis/*pharmacology
PMC - PMC4208094
MID - EMS60234
OID - NLM: EMS60234
EDAT- 2014/10/15 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/10/30
CRDT- 2014/10/15 06:00
PHST- 2014/02/23 00:00 [received]
PHST- 2014/09/01 00:00 [accepted]
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/10/30 00:00 [pmc-release]
AID - ncomms6116 [pii]
AID - 10.1038/ncomms6116 [doi]
PST - epublish
SO  - Nat Commun. 2014 Oct 14;5:5116. doi: 10.1038/ncomms6116.