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.
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, 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.
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.
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.
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.
Drosophila HNF4 directs a developmental switch at the onset of adulthood that suppresses diabetes by promoting mitochondrial function and supporting glucose-stimulated insulin secretion.
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.