GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_26632
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization.
Périodique
Journal of Clinical Investigation
Auteur(s)
Burcelin R., Crivelli V., Perrin C., Da Costa A., Mu J., Kahn B.B., Birnbaum M.J., Kahn C.R., Vollenweider P., Thorens B.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
111
Numéro
10
Pages
1555-1562
Langue
anglais
Résumé
Recent evidence suggests the existence of a hepatoportal vein glucose sensor, whose activation leads to enhanced glucose use in skeletal muscle, heart, and brown adipose tissue. The mechanism leading to this increase in whole body glucose clearance is not known, but previous data suggest that it is insulin independent. Here, we sought to further determine the portal sensor signaling pathway by selectively evaluating its dependence on muscle GLUT4, insulin receptor, and the evolutionarily conserved sensor of metabolic stress, AMP-activated protein kinase (AMPK). We demonstrate that the increase in muscle glucose use was suppressed in mice lacking the expression of GLUT4 in the organ muscle. In contrast, glucose use was stimulated normally in mice with muscle-specific inactivation of the insulin receptor gene, confirming independence from insulin-signaling pathways. Most importantly, the muscle glucose use in response to activation of the hepatoportal vein glucose sensor was completely dependent on the activity of AMPK, because enhanced hexose disposal was prevented by expression of a dominant negative AMPK in muscle. These data demonstrate that the portal sensor induces glucose use and development of hypoglycemia independently of insulin action, but by a mechanism that requires activation of the AMPK and the presence of GLUT4.
Mots-clé
Adenylate Kinase, Adipose Tissue, Animals, Blood Glucose, Deoxyglucose, Diaphragm, Genes, Dominant, Glucose, Glucose Transporter Type 4, Infusions, Intravenous, Insulin, Liver, Mice, Mice, Knockout, Mice, Transgenic, Monosaccharide Transport Proteins, Muscle Proteins, Muscle, Skeletal, Myocardium, Organ Specificity, Portal Vein, Receptor, Insulin, Signal Transduction, Skin
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:23
Dernière modification de la notice
20/08/2019 13:05
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