Kinetics of GLUT4 trafficking in rat and human skeletal muscle.
OBJECTIVE
In skeletal muscle, insulin stimulates glucose transport activity three- to fourfold, and a large part of this stimulation is associated with a net translocation of GLUT4 from an intracellular compartment to the cell surface. We examined the extent to which insulin or the AMP-activated protein kinase activator AICAR can lead to a stimulation of the exocytosis limb of the GLUT4 translocation pathway and thereby account for the net increase in glucose transport activity.


METHODS
Using a biotinylated photoaffinity label, we tagged endogenous GLUT4 and studied the kinetics of exocytosis of the tagged protein in rat and human skeletal muscle in response to insulin or AICAR. Isolated epitrochlearis muscles were obtained from male Wistar rats. Vastus lateralis skeletal muscle strips were prepared from open muscle biopsies obtained from six healthy men (age 39 +/- 11 years and BMI 25.8 +/- 0.8 kg/m2).


RESULTS
In rat epitrochlearis muscle, insulin exposure leads to a sixfold stimulation of the GLUT4 exocytosis rate (with basal and insulin-stimulated rate constants of 0.010 and 0.067 min(-1), respectively). In human vastus lateralis muscle, insulin stimulates GLUT4 translocation by a similar sixfold increase in the exocytosis rate constant (with basal and insulin-stimulated rate constants of 0.011 and 0.075 min(-1), respectively). In contrast, AICAR treatment does not markedly increase exocytosis in either rat or human muscle.


CONCLUSIONS
Insulin stimulation of the GLUT4 exocytosis rate constant is sufficient to account for most of the observed increase in glucose transport activity in rat and human muscle.
Karlsson
Håkan K R
HK
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Chibalin
Alexander V
AV
Koistinen
Heikki A
HA
Yang
Jing
J
Koumanov
Francoise
F
Wallberg-Henriksson
Harriet
H
Zierath
Juleen R
JR
Holman
Geoffrey D
GD
D000328:Adult; D000818:Animals; D001706:Biopsy; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport; D051381:Rats
D051275:Glucose Transporter Type 4; D007328:Insulin; D010750:Phosphoproteins; C495692:SLC2A4 protein, human; C495694:Slc2a4 protein, rat; D005947:Glucose