title: The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.
abstract: BACKGROUND
  An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance. Laminitis, failure of the weightbearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs), responsible for glucose uptake, is central to the dysregulation of glucose metabolism and may play a role in the pathophysiology of laminitis.
  
  
  OBJECTIVE
  We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during marked and moderate hyperinsulinaemia.
  
  
  METHODS
  Randomised, controlled study.
  
  
  METHODS
  Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged euglycaemic-hyperinsulinaemic clamp or a prolonged glucose infusion, and results were compared with those of electrolyte-treated control animals. Protein expression of GLUTs was examined with immunoblotting.
  
  
  RESULTS
  Lamellar tissue contained more GLUT1 protein than skeletal muscle (P = 0.002) and less GLUT4 than the heart (P = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the prolonged euglycaemic-hyperinsulinaemic clamp), GLUT1 protein expression was decreased in skeletal muscle (P = 0.029) but unchanged in the lamellae, while novel GLUTs (8 and 12) were increased in the lamellae (P = 0.03) but not in skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the prolonged glucose infusion) did not cause differential GLUT protein expression in the lamellae compared with control horses.
  
  
  CONCLUSIONS
  The results suggest that lamellar tissue functions independently of insulin and that insulin resistance may not be an essential component of the aetiology of laminitis. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation.
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: de Laat
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Clement
authors.affiliation: Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Australia.
authors.forename: M N
authors.initials: MN
authors.lastname: Sillence
authors.affiliation: Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Neston, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: McGowan
authors.affiliation: Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Pollitt
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Lacombe
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000662:veterinary; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D006736:Horses / Q000378:metabolism*; D006946:Hyperinsulinism / Q000662:veterinary*; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D005947:Glucose
keywords: glucose transporter; horse; insulin; insulin resistance; laminitis