Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs

Minoru Horie, Ayako Ishida-Takahashi, Tomohiko Ai, Toshihisa Nishimoto, Yoshiyuki Tsuura, Hitoshi Ishida, Yutaka Seino, Shigetake Sasayama

Research output: Contribution to journalReview article

11 Scopus citations

Abstract

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 β-cells by inhibiting ATP-sensitive K+ (K(ATP)) channels in a manner similar to sulfonylurea drugs. The mechanism underlying block of K(ATP), 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 K(ATP), channels in β-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 (Kit6.2). Antiarrhythmic drugs reversibly inhibit the K+ conductance displayed by the Kit6.1 (a putative K(ATP) channel clone)- transfected NIH3T3 cells. Therefore they appear to interact directly with the pore-forming subunit, thereby inhibiting K(ATP) channel currents and exerting an insulinotrophic effect.

Original languageEnglish (US)
Pages (from-to)69-72
Number of pages4
JournalCardiovascular research
Volume34
Issue number1
DOIs
StatePublished - Apr 1 1997
Externally publishedYes

Keywords

  • ATP sensitive
  • Antiarrhythmic drugs
  • Potassium channel
  • Sulfonylureas

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Horie, M., Ishida-Takahashi, A., Ai, T., Nishimoto, T., Tsuura, Y., Ishida, H., Seino, Y., & Sasayama, S. (1997). Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs. Cardiovascular research, 34(1), 69-72. https://doi.org/10.1016/S0008-6363(97)00014-X