Miniglucagon (glucagon 19-29): a novel regulator of the pancreatic islet physiology.
Miniglucagon, the COOH-terminal (19-29) fragment processed from glucagon, is a potent and efficient inhibitor of insulin secretion from the MIN 6 beta-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 alpha-cells. Using confocal and electron microscopy analysis, we observed that miniglucagon is colocalized with glucagon in mature secretory granules of alpha-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 beta-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 beta-cell would result in an impaired insulin secretion, as observed in type 2 diabetes.
Dalle
Stéphane
S
Institut National de la Santé et de la Recherche Médicale, Montpellier, France.
Fontés
Ghislaine
G
Lajoix
Anne-Dominique
AD
LeBrigand
Laurence
L
Gross
René
R
Ribes
Gérard
G
Dufour
Michel
M
Barry
Léo
L
LeNguyen
Dung
D
Bataille
Dominique
D
D000818:Animals; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007106:Immune Sera / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D007106:Immune Sera; D007328:Insulin; D010446:Peptide Fragments; C039265:glucagon (19-29); D005934:Glucagon