14 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. 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

    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

    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. 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. 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.
    1. Cell Biology

    Potassium dependent rescue of a myopathy with core-like structures in mouse

    M Gartz Hanson, Jonathan J Wilde ... Lee Niswander
    A mouse model of human muscle myopathy is used to provide mechanistic insight, identify possible biomarkers of disease, and suggest possible therapeutic strategies to alleviate muscle weakness.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults

    William E Barry, Carl S Thummel
    Drosophila HNF4 directs a developmental switch at the onset of adulthood that suppresses diabetes by promoting mitochondrial function and supporting glucose-stimulated insulin secretion.
    1. Neuroscience

    Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease

    Jeremy F Atherton, Eileen L McIver ... Mark D Bevan
    In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.

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