Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.

Détails

ID Serval
serval:BIB_D84CBC02FD9B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.
Périodique
Journal of Biological Chemistry
Auteur(s)
Thorens B., Guillam M.T., Beermann F., Burcelin R., Jaquet M.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2000
Volume
275
Numéro
31
Pages
23751-23758
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse alpha to beta cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic beta cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of alpha to beta cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in beta cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.
Mots-clé
Animals, Blood Glucose/analysis, Body Weight, Genes, Lethal, Genetic Complementation Test, Glucagon/blood, Glucagon/genetics, Glucose/metabolism, Glucose/pharmacology, Glucose Clamp Technique, Glucose Tolerance Test, Glucose Transporter Type 1, Glucose Transporter Type 2, Glucose Transporter Type 4, Insulin/blood, Insulin/genetics, Islets of Langerhans/cytology, Islets of Langerhans/drug effects, Mice, Mice, Mutant Strains, Mice, Transgenic, Monosaccharide Transport Proteins/biosynthesis, Monosaccharide Transport Proteins/deficiency, Muscle Proteins, RNA, Messenger/analysis, Tissue Distribution
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:41
Dernière modification de la notice
20/08/2019 16:57
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