Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfony...

A t 30,000 feet, ATP-sensitive potassium (KATP) channels are seen coupling the metabolic status of the cell to its electrical excitability. But down at the molecular level of the b-cell, there is a lot more coupling going on in exactly how the KATP channel does this. Coupling is developed in the conceptual framework of linkage (1), which thermodynamically quantifies how conformational states of...

The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmeta...

The present study investigated the localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity. Membrane fractionation based on the giant vesicle technique or the sucrose-gradient technique in combination with Western blotting demonstrated that the KATP channels are ...

Cardiomyopathies have been indicated to be one of the leading causes of heart failure. Though it was indicated that genetic defects, viral infection and trace element deficiency were among the causes of cardiomyopathy, the etiology has remained to be fully elucidated. Cardiomyocytes require large amounts of energy to maintain their normal biological functions. Adenosine triphosphate-sensitive p...