title: Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses.
abstract: Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4) and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039±0.0012 mmol/kg/min and M-to-I ratio (100×) 0.014±0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7±0.78 mmol/L) and hyperinsulinaemia (208±26.1 μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e., laminitis) in horses may be at or below a serum concentration of ∼200 μIU/mL.
authors.affiliation: Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. m.delaat@uq.edu.au
authors.forename: Melody A
authors.initials: MA
authors.lastname: de Laat
authors.forename: Martin N
authors.initials: MN
authors.lastname: Sillence
authors.forename: Catherine M
authors.initials: CM
authors.lastname: McGowan
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Pollitt
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004334:Drug Administration Schedule; D005534:Foot Diseases / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D006724:Hoof and Claw; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses; D006946:Hyperinsulinism / Q000139:chemically induced / Q000150:complications / Q000662:veterinary*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D007333:Insulin Resistance; D008297:Male
chemical_list: D001786:Blood Glucose; D005947:Glucose