1. Miniglucagon (glucagon 19-29): a novel regulator of the pancreatic islet physiology.
- Author
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Dalle S, Fontés G, Lajoix AD, LeBrigand L, Gross R, Ribes G, Dufour M, Barry L, LeNguyen D, and Bataille D
- Subjects
- Animals, Fluorescent Antibody Technique, Glucagon immunology, Glucagon metabolism, Immune Sera pharmacology, In Vitro Techniques, Insulin metabolism, Insulin Secretion, Islets of Langerhans metabolism, Islets of Langerhans ultrastructure, Male, Microscopy, Electron, Peptide Fragments immunology, Peptide Fragments metabolism, Rats, Rats, Wistar, Glucagon physiology, Islets of Langerhans physiology, Peptide Fragments physiology
- Abstract
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.
- Published
- 2002
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