β-Cell Secretory Products Activate α-Cell ATP-Dependent Potassium Channels to Inhibit Glucagon Release

  1. Isobel Franklin1,
  2. Jesper Gromada2,
  3. Asllan Gjinovci1,
  4. Sten Theander1 and
  5. Claes B. Wollheim1
  1. 1Department of Cell Physiology and Metabolism, University Medical Centre, Geneva, Switzerland
  2. 2Lilly Research Laboratories, Hamburg, Germany
  1. Address correspondencereprint requests to Dr. Claes B. Wollheim, Department of Cell PhysiologyMetabolism, University Medical Centre, 1211 Geneva 4, Switzerland. E-mail: claes.wollheim{at}


Glucagon, secreted from islet α-cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of β-cell secretory products zinc and insulin on isolated rat α-cells, intact islets, and perfused pancreata. Islet glucagon secretion was markedly zinc sensitive (IC50 = 2.7 μmol/l) more than insulin release (IC50 = 10.7 μmol/l). Glucose, the mitochondrial substrate pyruvate, and the ATP-sensitive K+ channel (KATP channel) inhibitor tolbutamide stimulated isolated α-cell electrical activity and glucagon secretion. Zinc opened KATP channels and inhibited both electrical activity and pyruvate (but not arginine)-stimulated glucagon secretion in α-cells. Insulin tran-siently increased KATP channel activity, inhibited electrical activity and glucagon secretion in α-cells, and inhibited pancreatic glucagon output. Insulin receptor and KATP channel subunit transcripts were more abundant in α- than β-cells. Transcript for the glucagon-like peptide 1 (GLP-1) receptor was not detected in α-cells nor did GLP-1 stimulate α-cell glucagon release. β-Cell secretory products zinc and insulin therefore inhibit glucagon secretion most probably by direct activation of KATP channels, thereby masking an α-cell metabolism secretion coupling pathway similar to β-cells.


  • J.G. is employed by and holds stock in Novo Nordisk.

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    • Accepted March 16, 2005.
    • Received January 26, 2005.
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