Glucose Dependence of Imidazoline-Induced Insulin Secretion

Different Characteristics of Two ATP-Sensitive K+ Channel–Blocking Compounds

  1. Claudia Bleck,
  2. Antje Wienbergen and
  3. Ingo Rustenbeck
  1. Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, Germany
  1. Address correspondence and reprint requests to Dr. I. Rustenbeck, Institute of Pharmacology and Toxicology, University of Braunschweig, Mendelssohnstrasse 1, D-38106 Braunschweig, Germany. E-mail: i.rustenbeck{at}


The glucose dependence of the insulinotropic action of KATP channel–blocking imidazoline compounds was investigated. Administration of 100 μmol/l phentolamine, but not 100 μmol/l efaroxan, markedly increased insulin secretion of freshly isolated mouse islets when the perifusion medium contained 5 mmol/l glucose. When the glucose concentration was raised to 10 mmol/l in the continued presence of either imidazoline, a clear potentiation of secretion occurred as compared with 10 mmol/l glucose alone. In the presence of efaroxan, a brisk first-phase–like increase was followed by a sustained phase, whereas a more gradual increase resulted in the presence of phentolamine. Administration of 100 μmol/l phentolamine was somewhat more effective than 100 μmol/l efaroxan to inhibit KATP channel activity in intact cultured β-cells (reduction by 96 vs. 83%). Both compounds were similarly effective to depolarize the β-cells. When measured by the perforated patch-technique, the depolarization by efaroxan was often oscillatory, whereas that by phentolamine was sustained. In perifused cultured islets, both compounds increased the cytosolic calcium concentration ([Ca2+]c) in the presence of 5 and 10 mmol/l glucose. Efaroxan induced large amplitude oscillations of [Ca2+]c, whereas phentolamine induced a sustained increase. It appears that a KATP channel block by imidazolines is not incompatible with a glucose-selective enhancement of insulin secretion. The glucose selectivity of efaroxan may involve an inhibitory effect distal to [Ca2+]c increase and/or the generation of [Ca2+]c oscillations.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    [Ca2+]c, cytosolic free calcium concentration; KATP channel, ATP-sensitive K+ channel.

    • Accepted May 27, 2004.
    • Received March 11, 2004.
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