Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs

Cardiovasc Res. 1997 Apr;34(1):69-72. doi: 10.1016/s0008-6363(97)00014-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3T3 Cells
  • ATP-Binding Cassette Transporters*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Potassium Channels / drug effects*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Drug / drug effects
  • Sulfonylurea Compounds / pharmacology*
  • Sulfonylurea Receptors


  • ATP-Binding Cassette Transporters
  • Anti-Arrhythmia Agents
  • Hypoglycemic Agents
  • Insulin
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors