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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 5116 (Oct 14 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25311795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Insulin
• KATP Channels
• Sulfonylurea Compounds

Topics

• Animals
• Biological Transport (drug effects, radiation effects)
• Cell Line
• Female
• Humans
• Hypoglycemic Agents (chemical synthesis, pharmacology)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, metabolism, radiation effects)
• Islets of Langerhans (drug effects, metabolism, radiation effects)
• KATP Channels (metabolism)
• Light
• Male
• Mice
• Mice, Inbred C57BL
• Sulfonylurea Compounds (chemical synthesis, pharmacology)