Abstract
Somatostatin inhibits glucagon-secretion from pancreatic alpha cells but its underlying mechanism is unknown. In mouse alpha cells, we found that somatostatin induced prominent hyperpolarization by activating a K+ channel, which was unaffected by tolbutamide but prevented by pre-treating the cells with pertussis toxin. The K+ channel was activated by intracellular GTP (with somatostatin), GTPgammaS or Gbetagamma subunits. It was thus identified as a G protein-gated K+ (K(G)) channel. RT-PCR and immunohistochemical analyses suggested the K(G) channel to be composed of Kir3.2c and Kir3.4. This study identified a novel ionic mechanism involved in somatostatin-inhibition of glucagon-secretion from pancreatic alpha cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Electrophysiology
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Female
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GTP-Binding Proteins / metabolism*
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Glucagon / metabolism
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Guanosine Triphosphate / pharmacology
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Immunohistochemistry
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Ion Channel Gating / physiology*
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Islets of Langerhans / drug effects*
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Mice
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Mice, Inbred Strains
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Patch-Clamp Techniques
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Pertussis Toxin
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Inwardly Rectifying*
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RNA, Messenger / metabolism
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Somatostatin / pharmacology*
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Tolbutamide / pharmacology
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Virulence Factors, Bordetella / pharmacology
Substances
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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RNA, Messenger
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Virulence Factors, Bordetella
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Somatostatin
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Guanosine Triphosphate
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Glucagon
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Tolbutamide
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Pertussis Toxin
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GTP-Binding Proteins
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Acetylcholine