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. Author manuscript; available in PMC: 2010 Jun 15.
Published in final edited form as: IUBMB Life. 2008 Mar;60(3):145–153. doi: 10.1002/iub.21

Figure 2.

Figure 2

Proposed model for the signaling pathways mediating fiber type transformation, mitochondrial biogenesis, and GLUT4 protein expression with skeletal muscle adaptations to endurance training. Exercise training leads to skeletal muscle fiber type transformation, mitochondrial biogenesis, and increased glucose transporter 4 (GLUT4) protein expression, and multiple signaling pathways have been suggested to be involved in these adaptations. Changes in the cellular energy status (AMP:ATP) stimulate AMP-activated protein kinase in the presence of the AMPK kinase, LKB1. AMPK may be involved in fiber type transformation, mitochondrial biogenesis, and GLUT4 biogenesis through increasing peroxisome-proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and probably also independent of PGC-1α. Exercise training-induced increases in PGC-1α are potentiated by a positive feedback loop through myocyte-enhancing factor 2 (MEF2) and are involved in fiber type transformation, mitochondrial biogenesis, and increased GLUT4 expression. Increases in intracellular Ca2+ levels lead to activation of the Ca2+/calmodulin-dependent phosphatase, calcineurin, as well as Ca2+/calmodulin-dependent protein kinases (CaMKs). While calcineurin is involved in a number of skeletal muscle adaptations, acting primarily through PGC-1α, a role of CaMKs has so far pointed toward increasing GLUT4 protein expression. Contraction-induced activation of p38 mitogen activated protein kinase (p38 MAPK) increases PGC-1α expression through activating transcription factor 2 (ATF2) and may therefore also be involved in skeletal muscle adaptations to exercise training.