Archive for the ‘MOLECULAR MECHANISMS’ Category
Signaling studies demonstrate that the underlying molecular mechanisms leading to the insulin- and physical activity-induced stimulation of glucose uptake in skeletal muscle are distinct. Winder and Hardie first published that adenosine monophosphate kinase (AMPK) was activated in type Ma muscle fibers during treadmill running. Since then AMPK’s role has been further delineated: it is a key energy-sensing/signaling protein of the skeletal muscle and has pleotropic effects. It is involved in:
Fatty acid oxidation
– AMPK phosphorylates and inactivates acetyl-CoA carboxylase, principally through the phosphorylation of serine79.
– This phosphorylation event is a molecular switch to increase fatty acid oxidation during muscular contraction. It also limits fatty acid biosynthesis during times of ATP and glucose depletion.
GLUT4 (glucose carrier) translocation
– Contraction of skeletal muscle enhances membrane glucose transport capacity by recruiting GLUT4 to the sarcolemma and T-tubules. Exercise training increases the expression of GLUT4 in skeletal muscle.
– The activation of AMPK by adenosine analog 5-aminoimidazole-4-carboxamide-1 -beta-D-ribofuranoside (AICAR) increases GLUT4 mRNA and protein expression in fast, but not slow, skeletal muscle.
– AICAR increases GLUT-4 mRNA through a transcriptional mechanism involving the interaction of myocyte enhancer factor-2 with 895 bp of the human GLUT-4 proximal promoter.
There are other mechanisms independent of either AMPK or insulin activation that enhance intracellular glucose uptake. Moreover, there is also likely to be more than a single exercise-signaling pathway. Physical activity increases the capacity of skeletal muscle to oxidize glucose and fatty acids.
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