title: Regulation of MAP kinase-directed mitogenic and protein kinase B-mediated signaling by cannabinoid receptor type 1 in skeletal muscle cells.
abstract: OBJECTIVE
  The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.
  
  
  METHODS
  Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.
  
  
  RESULTS
  Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.
  
  
  CONCLUSIONS
  Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism.
authors.affiliation: Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee, Scotland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lipina
authors.forename: Clare
authors.initials: C
authors.lastname: Stretton
authors.forename: Simon
authors.initials: S
authors.lastname: Hastings
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Hundal
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Irving
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Hundal
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005784:Gene Amplification; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007668:Kidney; D007739:L Cells / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D032446:Myoblasts / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017931:DNA Primers; D007328:Insulin; D043884:Receptor, Cannabinoid, CB1; D012313:RNA; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases