The centipede peptide toxin SpTx1 blocks the pore of ATP-sensitive potassium channels in pancreatic β cells to markedly enhance insulin secretion and mitigate hyperglycemia in diabetic mice insensitive to the anti-diabetic sulfonylurea glibenclamide.
Live cell imaging shows that the cAMP-sensor Epac2, a target of major antidiabetic drugs, is central to fusion pore control during insulin granule exocytosis.
Gregory M Martin, Balamurugan Kandasamy ... Show-Ling Shyng
A structure of a pancreatic ATP-sensitive potassium channel complex at 3.63Å resolution obtained by cryo-electron microscopy reveals how a commonly used anti-diabetic drug interacts with and inhibits the channel to stimulate insulin secretion.
Gregory M Martin, Min Woo Sung ... Show-Ling Shyng
Diverse KATP channel inhibitors occupy a common binding pocket and stabilize an interaction between Kir6.2 and SUR1 to allosterically control gating and promote the assembly and trafficking of nascent channels.
Gregory M Martin, Craig Yoshioka ... Show-Ling Shyng
Single-particle cryo-electron microscopy reveals the first subnanometer structure of ATP-sensitive potassium (KATP) channels, which provides insight into the structural mechanisms of channel assembly and gating.
Electron cryo-microscopy has revealed the three-dimensional structure of a potassium channel that has a central role in regulating the release of insulin from the pancreas.
Michael Puljung, Natascia Vedovato ... Frances Ashcroft
A combined FRET- and electrophysiology-based approach is used to study ATP/ADP ADP binding to the stimulatory nucleotide binding site of ATP-sensitive K+ channels and investigate their activation mechanism.
Richard J Lindsay, Michael J Kershaw ... Ivana Gudelj
Cooperation theory and a novel synthetic infection system provides a mechanistic understanding of why a seemingly successful disease management strategy can have devastating consequences for infected hosts.