Glucose uptake, utilization, and signaling in GLUT2-null islets.

Détails

ID Serval
serval:BIB_BEBAF46EA3DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glucose uptake, utilization, and signaling in GLUT2-null islets.
Périodique
Diabetes
Auteur(s)
Guillam M.T., Dupraz P., Thorens B.
ISSN
0012-1797[print], 0012-1797[linking]
Statut éditorial
Publié
Date de publication
09/2000
Volume
49
Numéro
9
Pages
1485-1491
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
We previously reported that pancreatic islet beta-cells from GLUT2-null mice lost the first phase but preserved the second phase of glucose-stimulated insulin secretion (GSIS). Furthermore, we showed that the remaining secretory activity required glucose uptake and metabolism because it can be blocked by inhibition of oxidative phosphorylation. Here, we extend these previous studies by analyzing, in GLUT2-null islets, glucose transporter isoforms and glucokinase expression and by measuring glucose usage, GSIS, and glucose-stimulated insulin mRNA biosynthesis. We show that in the absence of GLUT2, no compensatory expression of either GLUT1 or GLUT3 is observed and that glucokinase is expressed at normal levels. Glucose usage by isolated islets was increased between 1 and 6 mmol/l glucose but was not further increased between 6 and 20 mmol/l glucose. Parallel GSIS measurements showed that insulin secretion was not stimulated between 2.8 and 6 mmol/l glucose but was increased by >4-fold between 6 and 20 mmol/l glucose. Stimulation by glucose of total protein and insulin biosynthesis was also markedly impaired in the absence of GLUT2. Finally, we re-expressed GLUT2 in GLUT2-null beta-cells using recombinant lentiviruses and demonstrated a restoration of normal GSIS. Together, these data show that in the absence of GLUT2, glucose can still be taken up by beta-cells, albeit at a low rate, and that this transport activity is unlikely to be attributed to GLUT1 or GLUT3. This uptake activity, however, is limiting for normal glucose utilization and signaling to secretion and translation. These data further demonstrate the key role of GLUT2 in murine beta-cells for glucose signaling to insulin secretion and biosynthesis.
Mots-clé
Animals, Cells, Cultured, Glucokinase/genetics, Glucose/metabolism, Glucose/pharmacology, Glucose Transporter Type 1, Glucose Transporter Type 2, Glucose Transporter Type 3, Glycolysis, Insulin/biosynthesis, Insulin/genetics, Islets of Langerhans/drug effects, Islets of Langerhans/physiology, Kinetics, Mice, Mice, Knockout, Monosaccharide Transport Proteins/deficiency, Monosaccharide Transport Proteins/genetics, Nerve Tissue Proteins, Signal Transduction/physiology, Transcription, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:41
Dernière modification de la notice
20/08/2019 15:33
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