scholarly journals Stimulation of Electrogenic Glucose Transport by Glycogen Synthase Kinase 3

2010 ◽  
Vol 26 (4-5) ◽  
pp. 641-646 ◽  
Author(s):  
Rexhep Rexhepaj ◽  
Miribane Dërmaku-Sopjani ◽  
Eva-Maria Gehring ◽  
Mentor Sopjani ◽  
Daniela S. Kempe ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Stimulation Of

scholarly journals Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo

Diabetes ◽  
2003 ◽  
Vol 52 (3) ◽  
pp. 588-595 ◽  
Author(s):  
D. B. Ring ◽  
K. W. Johnson ◽  
E. J. Henriksen ◽  
J. M. Nuss ◽  
D. Goff ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

scholarly journals Use of lithium and SB-415286 to explore the role of glycogen synthase kinase-3 in the regulation of glucose transport and glycogen synthase

2003 ◽  
Vol 270 (18) ◽  
pp. 3829-3838 ◽  
Author(s):  
Katrina MacAulay ◽  
Eric Hajduch ◽  
Anne S. Blair ◽  
Matthew P. Coghlan ◽  
Stephen A. Smith ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

scholarly journals Cell-Extracellular Matrix Interactions Stimulate the AP-1 Transcription Factor in an Integrin-Linked Kinase- and Glycogen Synthase Kinase 3-Dependent Manner

1999 ◽  
Vol 19 (11) ◽  
pp. 7420-7427 ◽  
Author(s):  
Armelle A. Troussard ◽  
Clara Tan ◽  
T. Nathan Yoganathan ◽  
Shoukat Dedhar
Keyword(s):  
Extracellular Matrix ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Negative Regulator ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Dependent Manner ◽  
Wild Type ◽  
Integrin Linked Kinase ◽  
Stimulation Of

ABSTRACT Integrin-mediated interactions of cells with components of the extracellular matrix regulate cell survival, cell proliferation, cell differentiation, and cell migration. Some of these physiological responses are regulated via activation of transcription factors such as activator protein 1 (AP-1). Integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase whose activity is rapidly and transiently stimulated by cell-fibronectin interactions as well as by insulin stimulation. ILK activates protein kinase B and inhibits the glycogen synthase kinase 3 (GSK-3) activity in a phosphatidylinositol-3-kinase (PI 3-kinase)-dependent manner. We now show that cell adhesion to fibronectin results in a rapid and transient stimulation of AP-1 activity. At the same time, the kinase activity of ILK is stimulated whereas that of GSK-3 is inhibited. This fibronectin-dependent activation of AP-1 activity is inhibited in a dose-dependent manner if the cells are transfected with wild-type GSK-3, and also by inhibitors of PI 3-kinase. Stable or transient overexpression of ILK results in a stimulation of AP-1 activity which is inhibited by cotransfection with wild-type GSK-3 and kinase-deficient ILK. Transient transfection of ILK in HEK-293 cells stimulates complex formation between an AP-1 consensus oligonucleotide and nuclear proteins containing c-jun. The formation of this complex is inhibited by cotransfection with active GSK-3 or kinase-deficient ILK, suggesting that ILK may regulate AP-1 activation by inhibiting GSK-3, which has previously been shown to be a negative regulator of AP-1. In the presence of serum, ILK has no effect on the phosphorylation of Ser-73 in the N-terminal transactivation domain of c-jun. These results demonstrate a novel signaling pathway for the adhesion-mediated stimulation of AP-1 transcriptional activity involving ILK and GSK-3 and the subsequent regulation of the c-jun–DNA interaction.

scholarly journals A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression

2008 ◽  
Vol 295 (3) ◽  
pp. C836-C843 ◽  
Author(s):  
Carolyn L. Buller ◽  
Robert D. Loberg ◽  
Ming-Hui Fan ◽  
Qihong Zhu ◽  
James L. Park ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Cell Types ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Glucose Transporter 1 ◽  
Glut1 Expression ◽  
Mutant Cells

Glucose transport is a highly regulated process and is dependent on a variety of signaling events. Glycogen synthase kinase-3 (GSK-3) has been implicated in various aspects of the regulation of glucose transport, but the mechanisms by which GSK-3 activity affects glucose uptake have not been well defined. We report that basal glycogen synthase kinase-3 (GSK-3) activity regulates glucose transport in several cell types. Chronic inhibition of basal GSK-3 activity (8–24 h) in several cell types, including vascular smooth muscle cells, resulted in an approximately twofold increase in glucose uptake due to a similar increase in protein expression of the facilitative glucose transporter 1 (GLUT1). Conversely, expression of a constitutively active form of GSK-3β resulted in at least a twofold decrease in GLUT1 expression and glucose uptake. Since GSK-3 can inhibit mammalian target of rapamycin (mTOR) signaling via phosphorylation of the tuberous sclerosis complex subunit 2 (TSC2) tumor suppressor, we investigated whether chronic GSK-3 effects on glucose uptake and GLUT1 expression depended on TSC2 phosphorylation and TSC inhibition of mTOR. We found that absence of functional TSC2 resulted in a 1.5-to 3-fold increase in glucose uptake and GLUT1 expression in multiple cell types. These increases in glucose uptake and GLUT1 levels were prevented by inhibition of mTOR with rapamycin. GSK-3 inhibition had no effect on glucose uptake or GLUT1 expression in TSC2 mutant cells, indicating that GSK-3 effects on GLUT1 and glucose uptake were mediated by a TSC2/mTOR-dependent pathway. The effect of GSK-3 inhibition on GLUT1 expression and glucose uptake was restored in TSC2 mutant cells by transfection of a wild-type TSC2 vector, but not by a TSC2 construct with mutated GSK-3 phosphorylation sites. Thus, TSC2 and rapamycin-sensitive mTOR function downstream of GSK-3 to modulate effects of GSK-3 on glucose uptake and GLUT1 expression. GSK-3 therefore suppresses glucose uptake via TSC2 and mTOR and may serve to match energy substrate utilization to cellular growth.

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