Lamellar events related to insulin‐like growth factor‐1 receptor signalling in two models relevant to endocrinopathic laminitis

Summary Background Insulin dysregulation, obesity, and exposure to high‐nonstructural carbohydrate (NSC) forage are risk factors for equine metabolic syndrome‐associated laminitis (EMSAL); high systemic insulin concentrations in EMSAL are proposed to induce cellular dysregulation in the digital lamellae through activation of the insulin‐like growth factor‐1 receptor. Objectives To use a dietary challenge model (DCM) and a euglycaemic–hyperinsulinaemic clamp (EHC) model to assess lamellar growth factor‐related signalling. Study design Lamellar phospho (P)‐protein concentrations of signalling proteins important in growth factor‐related signalling were assessed in 2 models: 1) lean and obese ponies on a low‐ or high‐NSC diet; and 2) EHC model using Standardbred horses. Methods Ponies stratified for body condition (lean [LN, n = 11] and obese [OB, n = 11]) were exposed to a low‐NSC diet (LO, n = 5 per group for LN LO and OB LO) or a high NSC diet (HI, n = 6 per group for LN HI and OB HI groups) for 7 days. For the EHC model, horses were administered insulin (constant rate infusion [6 mIU/kg bwt/min] combined with 50% dextrose, EHC group, n = 8)] or saline (0.57 mL/kg bwt/h, CON group, n = 8) for 48 h. Immunoblotting was employed to assess concentrations of activated/phosphorylated and total protein for members of the PI3K/Akt/mTORC1 and Ras/ERK pathways in lamellar samples from both models. Results In the DCM, lamellar P‐(Ser 240/244) RPS6 was increased in OB HI ponies (vs. OB LO, P