The alpha-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro

AMP-activated protein kinase (AMPK) is a key signaling protein in the regulation of skeletal muscle glucose uptake, but its role in mediating contraction-induced glucose transport is still debated. The effect of contraction on glucose transport is impaired in EDL muscle of transgenic mice expressing...

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Published in:American journal of physiology: endocrinology and metabolism 2008-12, Vol.295 (6), p.E1447-E1454
Main Authors: Lefort, Natalie, St-Amand, Emmanuelle, Morasse, Sébastien, Côté, Claude H, Marette, André
Format: Article
Language:English
Subjects:
Aminoimidazole Carboxamide - analogs & derivatives
Aminoimidazole Carboxamide - pharmacology
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
AMP-Activated Protein Kinases - physiology
Animals
Biological Transport - drug effects
Biological Transport - genetics
Glucose - metabolism
Mice
Mice, Knockout
Muscle Contraction - genetics
Muscle Contraction - physiology
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Physical Stimulation
Ribonucleotides - pharmacology
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Summary:AMP-activated protein kinase (AMPK) is a key signaling protein in the regulation of skeletal muscle glucose uptake, but its role in mediating contraction-induced glucose transport is still debated. The effect of contraction on glucose transport is impaired in EDL muscle of transgenic mice expressing a kinase-dead, dominant negative form of the AMPKalpha(2) subunit (KD-AMPKalpha(2) mice). However, maximal force production is reduced in this muscle, raising the possibility that the defect in glucose transport was due to a secondary decrease in force production and not impaired AMPKalpha(2) activity. Generation of force-frequency curves revealed that muscle force production is matched between wild-type (WT) and KD-AMPKalpha(2) mice at frequencies < or =50 Hz. Moreover, AMPK activation is already maximal at 50 Hz in muscles of WT mice. When EDL muscles from WT mice were stimulated at a frequency of 50 Hz for 2 min (200-ms train, 1/s, 30 volts), contraction caused an approximately 3.5-fold activation of AMPKalpha(2) activity and an approximately 2-fold stimulation of glucose uptake. Conversely, whereas force production was similar in EDL of KD-AMPKalpha(2) animals, no effect of contraction was observed on AMPKalpha(2) activity, and glucose uptake stimulation was reduced by 50% (P < 0.01) As expected, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranosyl 5'-monophosphate (AICAR) caused a 2.3-fold stimulation of AMPKalpha(2) activity and a 1.7-fold increase in glucose uptake in EDL from WT mice, whereas no effect was detected in muscle from KD-AMPKalpha(2) mice. These data demonstrate that AMPK activation is essential for both AICAR and submaximal contraction-induced glucose transport in skeletal muscle but that AMPK-independent mechanisms are also involved.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.90362.2008