Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM; 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM; 1,430 μIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using ³H-thymidine as a marker, it was also demonstrated that insulin and IGF-1–stimulated cell proliferation in lamellar explants over the same concentration range as each other (1–100 nM), implying that each peptide acts via its own receptor (P < 0.001). Conversely, the effect of both peptides could be blocked using a selective anti-IGF-1R mAb (P < 0.001), implying that insulin acts via IGF1-R (either directly or indirectly). Notwithstanding this conundrum, the results demonstrate that insulin acts directly on lamellar tissue and suggest that a therapeutic anti-IGF-1R mAb could be useful in treating or preventing endocrinopathic laminitis.

尽管众所周知，高浓度胰岛素可引发马内分泌性蹄叶炎，但尚不清楚这是否代表通过胰岛素受体 (InsR) 对板层组织的直接作用、与 IGF-1 受体 (IGF-1R) 的相互作用，或其他一些间接的行动。这种不确定性是因为据报道层状组织中 InsR 的稀缺性以及胰岛素对马 IGF-1R 的低亲和力。在本研究中，使用从健康马的蹄中分离并在细胞培养基中培养 2 分钟至 48 小时的层状外植体来检查胰岛素和 IGF-1（作为阳性对照）的作用。在该系统中，低生理浓度的 IGF-1（10 nM；1.31 ng/mL）导致 5 分钟后磷酸化 IGF-1R 的出现显着增加（P< 0.05)，这种作用被人抗 IGF-1R 单克隆抗体 (mAb) 阻断。然而，高浓度的胰岛素（10 nM；1,430 μIU/mL）似乎会在 5 分钟（P < 0.01）、15 分钟和 30 分钟（P < 0.001）后引起 IGF-1R 的去磷酸化。使用³ H-胸苷作为标记物，还证明胰岛素和 IGF-1 在彼此相同的浓度范围内（1-100 nM）刺激层状外植体中的细胞增殖，这意味着每种肽通过其自身的受体起作用( P < 0.001)。相反，使用选择性抗 IGF-1R mAb 可以阻断两种肽的作用（P< 0.001)，暗示胰岛素通过 IGF1-R（直接或间接）起作用。尽管存在这个难题，但结果表明胰岛素直接作用于层状组织，并表明治疗性抗 IGF-1R mAb 可用于治疗或预防内分泌性椎板炎。