Document Detail


Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs.
MedLine Citation:
PMID:  9217874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiovascular drugs such as antiarrhythmic agents with Vaughan Williams class Ia action have been found to induce a sporadic hypoglycemia. Recent investigation has revealed that these drugs induce insulin secretion from pancreatic beta-cells by inhibiting ATP-sensitive K+ (KATP) channels in a manner similar to sulfonylurea drugs. The mechanism underlying block of KATP channels by antiarrhythmic drugs was different, however, from that of sulfonylureas: firstly, because binding of radioactive glibenclamide could not be inhibited by unlabelled antiarrhythmic agents, and vice versa; secondly, because the two compounds differ in the kinetics and sidedness of drug action-antiarrhythmic drugs act on the channel from the inner surface of the cell membrane, whereas glibenclamide binds through the intramembrane pathway; finally, it was shown that functional KATP channels in beta-cells are composed of two distinct molecules-a sulfonylurea receptor (SUR) and a channel pore-forming subunit, an inwardly-rectifying K channel with two transmembrane regions (Kir6.2). Antiarrhythmic drugs reversibly inhibit the K+ conductance displayed by the Kir6.1 (a putative KATP channel clone)-transfected NIH3T3 cells. Therefore they appear to interact directly with the pore-forming subunit, thereby inhibiting KATP channel currents and exerting an insulinotrophic effect.
Authors:
M Horie; A Ishida-Takahashi; T Ai; T Nishimoto; Y Tsuura; H Ishida; Y Seino; S Sasayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cardiovascular research     Volume:  34     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-08-11     Completed Date:  1997-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  69-72     Citation Subset:  IM    
Affiliation:
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan. horie@kuhp.kyoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
ATP-Binding Cassette Transporters*
Animals
Anti-Arrhythmia Agents / pharmacology*
Humans
Hypoglycemic Agents / pharmacology*
Insulin / secretion*
Islets of Langerhans / drug effects,  secretion*
Mice
Potassium Channels / drug effects*
Potassium Channels, Inwardly Rectifying*
Receptors, Drug / drug effects
Sulfonylurea Compounds / pharmacology*
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Anti-Arrhythmia Agents; 0/Hypoglycemic Agents; 0/Potassium Channels; 0/Potassium Channels, Inwardly Rectifying; 0/Receptors, Drug; 0/Sulfonylurea Compounds; 0/sulfonylurea receptor; 11061-68-0/Insulin

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