Membrane ion channels and diabetes.
Type-2, or non-insulin-dependent diabetes mellitus is a serious disease that is now widespread throughout Western society. Glucose intolerance, or failure of glucose to stimulate insulin secretion, is a primary factor in the manifestation of this disease and is likely to be due to the failure of glucose metabolism to stimulate pancreatic beta-cell electrical activity, calcium influx, and insulin secretion. In this review we describe how ion channels regulate the electrical behaviour of the beta-cell and how the membrane potential depolarises in response to a rise in glucose metabolism. Central to these electrical events is the inhibition of ATP-sensitive potassium channel by ATP, and we summarise recent advances in our understanding of the properties of this ion channel in coupling beta-cell metabolism to electrical activity. We discuss the mechanism, specificity, and clinical implications of the pharmacological inhibition of KATP channels by sulphonyureas and other antidiabetic drugs. The roles of other ion channels in regulating electrical activity are considered, and also their potential use as targets for drug action in treating beta-cell disorders.
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia. peter.proks@physiol.ox.ac.uk
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Proks
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Lippiat
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D008954:Models, Biological; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D007473:Ion Channels; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds