title: Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle.
abstract: BACKGROUND
  Insulin resistance (IR) has been widely recognized in humans, and more recently in horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin-sensitive tissues. Although the downstream signaling pathways regulating GLUT translocation are not well defined, AS160 recently has emerged as a potential key component. In addition, the role of GLUT12, one of the most recently identified insulin-sensitive GLUTs, during IR is unknown.
  
  
  OBJECTIVE
  We hypothesized that cell-surface GLUT will be decreased in muscle by an AS160-dependent pathway in horses with IR.
  
  
  METHODS
  Insulin-sensitive (IS) or IR mares (n = 5/group).
  
  
  METHODS
  Muscle biopsies were performed in mares classified as IS or IR based on results of an insulin-modified frequently sampled IV glucose tolerance test. By an exofacial bis-mannose photolabeled method, we specifically quantified active cell-surface GLUT4 and GLUT12 transporters. Total GLUT4 and GLUT12 and AS160 protein expression were measured by Western blots.
  
  
  RESULTS
  IR decreased basal cell-surface GLUT4 expression (P= .027), but not GLUT12, by an AS160-independent pathway, without affecting total GLUT4 and GLUT12 content. Cell-surface GLUT4 was not further enhanced by insulin stimulation in either group.
  
  
  CONCLUSIONS
  IR induced defects in the skeletal muscle glucose transport pathway by decreasing active cell-surface GLUT4.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Waller
authors.forename: T A
authors.initials: TA
authors.lastname: Burns
authors.forename: M C
authors.initials: MC
authors.lastname: Mudge
authors.forename: J K
authors.initials: JK
authors.lastname: Belknap
authors.forename: V A
authors.initials: VA
authors.lastname: Lacombe
mesh_terms: D000818:Animals; D005260:Female; D005951:Glucose Tolerance Test / Q000662:veterinary; D051246:Glucose Transport Proteins, Facilitative / Q000032:analysis / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000032:analysis / Q000378:metabolism; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D007328:Insulin