Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors.

Détails

ID Serval
serval:BIB_B43DE522929C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors.
Périodique
Journal of Clinical Investigation
Auteur(s)
Preitner F., Ibberson M., Franklin I., Binnert C., Pende M., Gjinovci A., Hansotia T., Drucker D.J., Wollheim C., Burcelin R., Thorens B.
ISSN
0021-9738[print], 0021-9738[linking]
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
113
Numéro
4
Pages
635-645
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The role of the gluco-incretin hormones GIP and GLP-1 in the control of beta cell function was studied by analyzing mice with inactivation of each of these hormone receptor genes, or both. Our results demonstrate that glucose intolerance was additively increased during oral glucose absorption when both receptors were inactivated. After intraperitoneal injections, glucose intolerance was more severe in double- as compared to single-receptor KO mice, and euglycemic clamps revealed normal insulin sensitivity, suggesting a defect in insulin secretion. When assessed in vivo or in perfused pancreas, insulin secretion showed a lack of first phase in Glp-1R(-/-) but not in Gipr(-/-) mice. In perifusion experiments, however, first-phase insulin secretion was present in both types of islets. In double-KO islets, kinetics of insulin secretion was normal, but its amplitude was reduced by about 50% because of a defect distal to plasma membrane depolarization. Thus, gluco-incretin hormones control insulin secretion (a) by an acute insulinotropic effect on beta cells after oral glucose absorption (b) through the regulation, by GLP-1, of in vivo first-phase insulin secretion, probably by an action on extra-islet glucose sensors, and (c) by preserving the function of the secretory pathway, as evidenced by a beta cell autonomous secretion defect when both receptors are inactivated.
Mots-clé
Animals, Blood Glucose/metabolism, Carbachol/metabolism, Cyclic AMP/metabolism, Female, Gastric Inhibitory Polypeptide/metabolism, Glucagon/metabolism, Glucagon-Like Peptide 1, Glucose Tolerance Test, Insulin/secretion, Male, Mice, Mice, Knockout, Pancreas/metabolism, Peptide Fragments/metabolism, Protein Precursors/metabolism, Receptors, Gastrointestinal Hormone/genetics, Receptors, Gastrointestinal Hormone/metabolism, Receptors, Glucagon/genetics, Receptors, Glucagon/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:41
Dernière modification de la notice
20/08/2019 15:22
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