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 journalArticle

11 Citations (Scopus)

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 1997
Externally publishedYes

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Anti-Arrhythmia Agents
Adenosine Triphosphate
Insulin
Glyburide
Sulfonylurea Receptors
Inwardly Rectifying Potassium Channel
Cardiovascular Agents
Hypoglycemia
Pharmaceutical Preparations
Pharmacokinetics
Clone Cells
Cell Membrane

Keywords

  • Antiarrhythmic drugs
  • ATP sensitive
  • Potassium channel
  • Sulfonylureas

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Horie, M., Ishida-Takahashi, A., Ai, T., Nishimoto, T., Tsuura, Y., Ishida, H., ... 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

Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs. / Horie, Minoru; Ishida-Takahashi, Ayako; Ai, Tomohiko; Nishimoto, Toshihisa; Tsuura, Yoshiyuki; Ishida, Hitoshi; Seino, Yutaka; Sasayama, Shigetake.

In: Cardiovascular Research, Vol. 34, No. 1, 04.1997, p. 69-72.

Research output: Contribution to journalArticle

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, vol. 34, no. 1, pp. 69-72. https://doi.org/10.1016/S0008-6363(97)00014-X
Horie, Minoru ; Ishida-Takahashi, Ayako ; Ai, Tomohiko ; Nishimoto, Toshihisa ; Tsuura, Yoshiyuki ; Ishida, Hitoshi ; Seino, Yutaka ; Sasayama, Shigetake. / Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs. In: Cardiovascular Research. 1997 ; Vol. 34, No. 1. pp. 69-72.
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