Recent studies have identified a high-affinity receptor on the plasma membrane of the β-cell that is specific for all of the sulfonylureas. The most potent secondgeneration drugs, glyburide and glipizide, bind to the receptor and trigger insulin release at nanomolar concentrations. The affinity to the receptor-ligand interaction of all sulfonylureas correlates with their potency as insulin secretagogues, further implicating receptor occupancy with signal transduction. These drugs also inhibit the electrical activity of ATPsensitive K+ channels and K+ efflux through these channels. The channels are also closed by the metabolism of the major insulin secretagogues, glucose and the amino acids, which signal insulin release by increasing the ATP level or the [ATP]-to-[ADP] ratio on the cytoplasmic side of the channel. Based on the channel number and the amount of K+ current they pass, it is possible to calculate that these channels control the resting membrane potential of the β-cell. Inactivation of the ATP-inhibitable K+ channel results in a fall in the resting membrane potential, cell depolarization, and influx of extracellular Ca2+ through the voltage-dependent Ca2+ channel. The rise in intracellular free Ca2+ level triggers exocytosis. Thus, it is now possible to link either a stimulus from the metabolism of insulin secretagogues or the sulfonylureas to ionic and electrical events that elicit insulin release. These data also suggest that the sulfonylurea receptor or a closely associated protein is an ATP-sensitive K+ channel.
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Perspectives in Diabetes| July 01 1988
Sulfonylurea Receptors, Ion Channels, and Fruit Flies
Aubrey E Boyd, III
Aubrey E Boyd, III
Division of Endocrinology and Metabolism, and the Diabetes and Endocrinology Research Center, the Departments of Medicine and Cell Biology, Baylor College of Medicine
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Address correspondence and reprint requests to A.E. Boyd III, MD, Chief of Endocrinology and Metabolism Division, Department of Internal Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
March 14 1988
March 22 1988
Aubrey E Boyd; Sulfonylurea Receptors, Ion Channels, and Fruit Flies. Diabetes 1 July 1988; 37 (7): 847–850. https://doi.org/10.2337/diab.37.7.847
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