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Kinetic Evidence for Unique Regulation of GLUT4 Trafficking by Insulin and AMP-activated Protein Kinase Activators in L6 Myotubes
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- In L6 myotubes, redistribution of a hemagglutinin (HA) epitope-tagged GLUT4 (HA-GLUT4) to the cell surface occurs rapidly in response to insulin stimulation and AMP-activated protein kinase (AMPK) activation. We have examined whether these separate signaling pathways have a convergent mechanism that leads to GLUT4 mobilization and to changes in GLUT4 recycling. HA antibody uptake on GLUT4 in the basal steady state reached a final equilibrium level that was only 81% of the insulin-stimulated level. AMPK activators (5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and A-769662) led to a similar level of antibody uptake to that found in insulin-stimulated cells. However, the combined responses to insulin stimulation and AMPK activation led to an antibody uptake level of approximately 20% above the insulin level. Increases in antibody uptake due to insulin, but not AICAR or A-769662, treatment were reduced by both wortmannin and Akt inhibitor. The GLUT4 internalization rate constant in the basal steady state was very rapid (0.43 min(-1)) and was decreased during the steady-state responses to insulin (0.18 min(-1)), AICAR (0.16 min(-1)), and A-769662 (0.24 min(-1)). This study has revealed a nonconvergent mobilization of GLUT4 in response to activation of Akt and AMPK signaling. Furthermore, GLUT4 trafficking in L6 muscle cells is very reliant on regulated endocytosis for control of cell surface GLUT4 levels.
- Subjects :
- Cell/Endocytosis
medicine.medical_specialty
medicine.medical_treatment
Muscle Fibers, Skeletal
Membrane/Recycling
Thiophenes
AMP-Activated Protein Kinases
Biochemistry
Cell Line
Wortmannin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
AMP-activated protein kinase
Internal medicine
medicine
Animals
Insulin
Protein kinase A
Molecular Biology
Protein kinase B
030304 developmental biology
0303 health sciences
Glucose Transporter Type 4
biology
Biphenyl Compounds
AMPK
Cell Biology
Membrane/Trafficking
Phosphorylation/Kinases/Serine-Threonine
Endocytosis
Enzyme Activation
Kinetics
Protein Transport
Membrane Transport, Structure, Function, and Biogenesis
Endocrinology
chemistry
Pyrones
Diseases/Diabetes
biology.protein
Cell/Exocytosis
Signal transduction
Hormones/Insulin
Transport/Glucose
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
GLUT4
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....3ea1d0a0ecf2ee23cb402d8b32527903