title: A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis.
abstract: The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged euglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24h) and acute (46 h) phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13-32-fold (P<0.05) at both time-points in the insulin-treated horses. A second aim was to determine if the down-regulation of the receptor genes could be accounted for by an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution. There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy for hyperinsulinaemic laminitis.
authors: Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. melody.de_Laat@okstate.edu
authors: Melody A
authors: MA
authors: de Laat
authors: Christopher C
authors: CC
authors: Pollitt
authors: Myat T
authors: MT
authors: Kyaw-Tanner
authors: Catherine M
authors: CM
authors: McGowan
authors: Martin N
authors: MN
authors: Sillence
mesh_terms: D000818:Animals; D001786:Blood Glucose; D005260:Female; D005534:Foot Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D006724:Hoof and Claw / Q000473:pathology*; D006734:Horse Diseases; D006736:Horses; D006946:Hyperinsulinism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: Equine; Insulin; Insulin-like growth factor-1 receptor; Laminitis