23 results found
    1. Neuroscience

    Blocking Kir6.2 channels with SpTx1 potentiates glucose-stimulated insulin secretion from murine pancreatic β cells and lowers blood glucose in diabetic mice

    Yajamana Ramu, Jayden Yamakaze ... Zhe Lu
    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.
    1. Cell Biology

    Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis

    Alenka Guček, Nikhil R Gandasi ... Sebastian Barg
    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.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM

    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.
    1. Structural Biology and Molecular Biophysics

    Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM

    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.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating

    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.
    1. Structural Biology and Molecular Biophysics

    Ion Channels: From ions to insulin

    Voula Kanelis
    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.
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    1. Structural Biology and Molecular Biophysics

    Activation mechanism of ATP-sensitive K+ channels explored with real-time nucleotide binding

    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.
    1. Structural Biology and Molecular Biophysics

    Nucleotide inhibition of the pancreatic ATP-sensitive K+ channel explored with patch-clamp fluorometry

    Samuel G Usher, Frances M Ashcroft, Michael C Puljung
    Simultaneous measurements of ligand binding and channel currents are used to understand gating of the ATP-sensitive K+ channel.
    1. Ecology

    Harbouring public good mutants within a pathogen population can increase both fitness and virulence

    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.
    1. Cell Biology

    P2Y1 purinergic receptor identified as a diabetes target in a small-molecule screen to reverse circadian β-cell failure

    Biliana Marcheva, Benjamin J Weidemann ... Joseph Bass
    A genetically sensitized drug screen identifies a circadian diabetes target and establishes a novel discovery pathway to treat β-cell failure.

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