Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise

IUBMB Life. 2008 Mar;60(3):145-53. doi: 10.1002/iub.21.


Physical activity elicits physiological responses in skeletal muscle that result in a number of health benefits, in particular in disease states, such as type 2 diabetes. An acute bout of exercise/muscle contraction improves glucose homeostasis by increasing skeletal muscle glucose uptake, while chronic exercise training induces alterations in the expression of metabolic genes, such as those involved in muscle fiber type, mitochondrial biogenesis, or glucose transporter 4 (GLUT4) protein levels. A primary goal of exercise research is to elucidate the mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we briefly summarize the current literature describing the molecular signals underlying skeletal muscle responses to acute and chronic exercise. The search for possible exercise/contraction-stimulated signaling proteins involved in glucose transport, muscle fiber type, and mitochondrial biogenesis is ongoing. Further research is needed because full elucidation of exercise-mediated signaling pathways would represent a significant step toward the development of new pharmacological targets for the treatment of metabolic diseases such as type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases
  • Adaptation, Physiological*
  • Calcineurin / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Exercise*
  • GTPase-Activating Proteins / metabolism
  • Glucose / metabolism
  • Heat-Shock Proteins
  • Humans
  • Multienzyme Complexes / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology*
  • Transcription Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • GTPase-Activating Proteins
  • Heat-Shock Proteins
  • Multienzyme Complexes
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • TBC1D4 protein, human
  • Transcription Factors
  • Protein-Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • Calcineurin
  • Glucose