The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases alpha and beta in skeletal muscle.
The AMP-activated protein kinase (AMPK) pathway participates in the metabolic effects of contraction on muscle glucose uptake. We have shown that contraction increases both GLUT4 translocation to the cell surface and p38 mitogen-activated protein kinase (p38 MAPK) activity. The latter pathway may be involved in the activation of GLUT4. Here we investigated whether the AMPK activator AICAR increases glucose uptake by inducing translocation of GLUT4 and/or by activating the p38 MAPK pathway. AICAR infusion into glucose-clamped rats increased muscle glucose uptake and GLUT4 translocation from an intracellular fraction to the plasma membrane but not to T-tubules. AICAR also caused recruitment of the transferrin receptor to the plasma membrane and increased [125I]-transferrin uptake in isolated muscle. AICAR treatment in vivo or in vitro activated both p38 MAPKalpha and beta (1.6- to 2.8-fold) in EDL muscles with a time course identical to that of stimulation of AMPK and glucose transport. The p38 MAPK inhibitor SB203580 abrogated the stimulatory effect of AICAR on glucose uptake. These results suggest that AICAR increases muscle glucose uptake by two mechanisms: 1) inducing selective recruitment of GLUT4 to the plasma membrane, and 2) activating p38 MAPKalpha and beta, which may be involved in the activation of GLUT4.
Lemieux
Kathleen
K
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, Québec, G1V 4G2, Canada.
Konrad
Daniel
D
Klip
Amira
A
Marette
André
A
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D046508:Culture Techniques; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D008297:Male; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology*; D012508:Sarcolemma / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012265:Ribonucleotides; C495694:Slc2a4 protein, rat; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose