Miniglucagon (Glucagon 19-29)

A Novel Regulator of the Pancreatic Islet Physiology

  1. Stéphane Dalle1,
  2. Ghislaine Fontés1,
  3. Anne-Dominique Lajoix2,
  4. Laurence LeBrigand1,
  5. René Gross2,
  6. Gérard Ribes2,
  7. Michel Dufour1,
  8. Léo Barry1,
  9. Dung LeNguyen1 and
  10. Dominique Bataille1
  1. 1Institut National de la Santé et de la Recherche Médicale, Montpellier, France
  2. 2Unité Mixte de Recherche du Centre National de la Recherche Scientifique, Institut de Biologie, Montpellier, France

    Abstract

    Miniglucagon, the COOH-terminal (19-29) fragment processed from glucagon, is a potent and efficient inhibitor of insulin secretion from the MIN 6 β-cell line. Using the rat isolated-perfused pancreas, we investigated the inhibitory effect of miniglucagon on insulin secretion and evaluated the existence of an inhibitory tone exerted by this peptide inside the islet. Miniglucagon dose-dependently inhibited insulin secretion stimulated by 8.3 mol/l glucose, with no change in the perfusion flow rate. A concentration of 1 nmol/l miniglucagon had a significant inhibitory effect on a 1 nmol/l glucagon-like peptide 1 (7-36) amide-potentiated insulin secretion. A decrease in extracellular glucose concentration simultaneously stimulated glucagon and miniglucagon secretion from pancreatic α-cells. Using confocal and electron microscopy analysis, we observed that miniglucagon is colocalized with glucagon in mature secretory granules of α-cells. Perfusion of an anti-miniglucagon antiserum directed against the biologically active moiety of the peptide resulted in a more pronounced effect of a glucose challenge on insulin secretion, indicating that miniglucagon exerts a local inhibitory tone on β-cells. We concluded that miniglucagon is a novel local regulator of the pancreatic islet physiology and that any abnormal inhibitory tone exerted by this peptide on the β-cell would result in an impaired insulin secretion, as observed in type 2 diabetes.

    Footnotes

    • Address correspondence and reprint requests to Dominique Bataille, the Institut National de la Santé et de la Recherche Médicale U 376, CHU Arnaud-de-Villeneuve, 34295 Montpellier, France. E-mail: bataille{at}montp.inserm.fr.

      Received for publication 11 July 2001 and accepted in revised form 7 November 2001.

      AUC, area under the curve; FITC, fluorescein isothiocyanate; GLP-1, glucagon-like peptide 1; HPLC, high-performance liquid chromatography; KRB, Krebs-Ringer bicarbonate; MGE, miniglucagon-generating endopeptidase; PBS, phosphate-buffered saline; tGLP-1, GLP-1 (7-36) amide.

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