title: Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis.
abstract: BACKGROUND
  One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels.
  
  
  OBJECTIVE
  Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies.
  
  
  METHODS
  Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3-kinase) and PD-098059 (to block MAP-kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min.
  
  
  RESULTS
  Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin-incubated and wortmannin-incubated rings.
  
  
  CONCLUSIONS
  This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP-kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions.
  
  
  CONCLUSIONS
  The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis.
authors.affiliation: Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA. cvenugopal@vetmed.lsu.edu
authors.forename: C S
authors.initials: CS
authors.lastname: Venugopal
authors.forename: S
authors.initials: S
authors.lastname: Eades
authors.forename: E P
authors.initials: EP
authors.lastname: Holmes
authors.forename: R E
authors.initials: RE
authors.lastname: Beadle
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D005528:Foot; D005534:Foot Diseases / Q000378:metabolism / Q000662:veterinary; D005552:Forelimb / Q000098:blood supply*; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014680:Veins / Q000187:drug effects* / Q000502:physiology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D007328:Insulin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D000077191:Wortmannin