Abstract
The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. We have isolated cDNA clones encoding rat Kir6.2. Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. Thus, decreased expression of Kir6.2 could contribute to the beta-cell dysfunction which characterizes diabetes mellitus in this animal model.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / pharmacology
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Amino Acid Sequence
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Animals
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Base Sequence
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Cattle
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Cell Line
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Cloning, Molecular
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DNA Primers
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Diabetes Mellitus / genetics
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Diabetes Mellitus / physiopathology*
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Diabetes Mellitus, Type 2 / genetics
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Diabetes Mellitus, Type 2 / physiopathology*
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Gene Expression*
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Glyburide / pharmacology
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Humans
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Islets of Langerhans / metabolism*
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Islets of Langerhans / physiopathology
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Male
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Obesity*
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Organ Specificity
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Polymerase Chain Reaction
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Potassium Channels / biosynthesis
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Potassium Channels / physiology*
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Potassium Channels, Inwardly Rectifying*
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Rats
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Rats, Zucker
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Reference Values
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Sequence Homology, Amino Acid
Substances
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DNA Primers
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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RNA, Messenger
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Recombinant Proteins
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Adenosine Triphosphate
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Glyburide