Details

Autor(en) / Beteiligte

• Dalle, Stéphane
• Fontés, Ghislaine
• Lajoix, Anne-Dominique
• LeBrigand, Laurence
• Gross, René
• Ribes, Gérard
• Dufour, Michel
• Barry, Léo
• LeNguyen, Dung
• Bataille, Dominique

Titel

Miniglucagon (Glucagon 19-29)

Ist Teil von

• Diabetes (New York, N.Y.), 2002-02, Vol.51 (2), p.406-412

Ort / Verlag

American Diabetes Association

Erscheinungsjahr

2002

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Miniglucagon (Glucagon 19-29) A Novel Regulator of the Pancreatic Islet Physiology Stéphane Dalle 1 , Ghislaine Fontés 1 , Anne-Dominique Lajoix 2 , Laurence LeBrigand 1 , René Gross 2 , Gérard Ribes 2 , Michel Dufour 1 , Léo Barry 1 , Dung LeNguyen 1 and Dominique Bataille 1 1 Institut National de la Santé et de la Recherche Médicale, Montpellier, France 2 Unité 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.