Glucokinase expression is regulated by ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation
Author(s) :
Baldini, Steffi F. [Auteur]
Steenackers, Agata [Auteur]
Olivier-Van Stichelen, Stéphanie [Auteur]
Mir, Anne-Marie [Auteur]
mortuaire, marlène [Auteur]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Guinez, Céline [Auteur]
Steenackers, Agata [Auteur]
Olivier-Van Stichelen, Stéphanie [Auteur]
Mir, Anne-Marie [Auteur]
mortuaire, marlène [Auteur]
Lefebvre, Tony [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Guinez, Céline [Auteur]
Journal title :
Biochemical and biophysical research communications
Abbreviated title :
Biochem. Biophys. Res. Commun.
Volume number :
478
Pages :
942-948
Publication date :
2016
ISSN :
1090-2104
English keyword(s) :
Fasting
siOGT
Humans
Liver
Mice, Inbred C57BL
Enzyme Stability
beta-N-Acetylhexosaminidases
Male
Acetylglucosamine
Glycosylation
N-Acetylglucosaminyltransferases
Glucose
Hep G2 Cells
Glucose metabolism
Animals
Mouse
Models, Biological
Glucokinase
Mice, Obese
O-GlcNAcylation
siOGT
Humans
Liver
Mice, Inbred C57BL
Enzyme Stability
beta-N-Acetylhexosaminidases
Male
Acetylglucosamine
Glycosylation
N-Acetylglucosaminyltransferases
Glucose
Hep G2 Cells
Glucose metabolism
Animals
Mouse
Models, Biological
Glucokinase
Mice, Obese
O-GlcNAcylation
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that ...
Show more >Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver.Show less >
Show more >Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver.Show less >
Language :
Anglais
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Submission date :
2020-02-12T15:11:46Z