title: Effects of the insulin-sensitizing drug pioglitazone and lipopolysaccharide administration on insulin sensitivity in horses.
abstract: BACKGROUND
  Obesity and insulin resistance increase the risk of laminitis in horses. Pioglitazone (PG) is an insulin-sensitizing drug used in humans that is absorbed after oral administration to horses.
  
  
  OBJECTIVE
  PG treatment will increase insulin sensitivity and transcript abundance of glucose and lipid transporters in adipose and skeletal muscle tissues.
  
  
  METHODS
  Sixteen lean, healthy horses.
  
  
  METHODS
  Eight horses were administered PG (1 mg/kg bodyweight PO) for 12 days before induction of insulin resistance through IV administration of lipopolysaccharide (LPS). Treated and untreated controls (CN; n = 8) were subjected to testing of peripheral insulin sensitivity and biopsies of both subcutaneous (nuchal ligament) adipose tissue and skeletal muscle before and after treatment, and 24 hours after LPS administration.
  
  
  RESULTS
  PG treatment did not improve basal insulin sensitivity (CNs: 1.4 ± 0.3, PG-treated: 1.9 ± 1.3; P > .4) or mitigate LPS-induced insulin resistance (CNs: 0.4 ± 0.3, PG-treated: 0.4 ± 0.3); however, transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissue.
  
  
  CONCLUSIONS
  Either a higher dose or longer treatment period might be required for physiological effects to be observed. PG is a novel therapeutic agent requiring further investigation in horses in order to determine treatment efficacy.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Suagee
authors.forename: B A
authors.initials: BA
authors.lastname: Corl
authors.forename: J G
authors.initials: JG
authors.lastname: Wearn
authors.forename: M V
authors.initials: MV
authors.lastname: Crisman
authors.forename: M W
authors.initials: MW
authors.lastname: Hulver
authors.forename: R J
authors.initials: RJ
authors.lastname: Geor
authors.forename: L J
authors.initials: LJ
authors.lastname: McCutcheon
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism; D006736:Horses / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000378:metabolism*; D000077205:Pioglitazone; D011897:Random Allocation; D045162:Thiazolidinediones / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008070:Lipopolysaccharides; D045162:Thiazolidinediones; D000077205:Pioglitazone