The effects of locally delivered insulin on equine hoof lamellar tissue [thesis]

Matias Castro Olivera
The equine hoof lamellar tissue is a highly specialized structure that plays a critical role in the suspensory apparatus of the distal phalanx (SADP). Failure of this normal attachment between distal phalanx and hoof is a major consequence of laminitis. Several conditions have been associated with laminitis in the past, but those related to insulin resistance (IR) or excess of glucocorticoids appear to be involved in the majority of the reported cases. The common factor in these conditions is
more » ... ese conditions is hyperinsulinemia. Besides the main role of insulin in regulating glucose metabolism, it is involved in diverse physiologic process such as vascular modulation and cellular growth and proliferation. The role of insulin in laminitis has been assessed by different authors and new experimental model has arisen recently to induce laminitis after systemic administration of high concentrations of the hormone. However, the exact mechanism involved in the pathophysiology of the disease remains unclear. Utilizing the minimally invasive technique of tissue microdialysis, this work aimed to evaluate the local effects of insulin, delivered in higher than normal concentrations into the lamellar interstitial fluid, by assessing the suggested potential mechanisms involved in this form of the disease: vasodilation, derangements of energy metabolism, and epidermal cellular proliferation. The latter was assessed using 5-ethynyl-2'-deoxyuridine (EdU), a novel marker of mitotic activity. Insulin was delivered locally to the forefeet of healthy, Standardbred horses using one of the limbs as treatment (n=6) and the contralateral as control (n=6). Although they did not reach significance, changes in lamellar glucose metabolism (decreased interstitial glucose) were observed after delivering an approximated amount of 0.5 µg/ml for 24h at 1 µL/min via microdialysis to the sublamellar tissue. No variations were detected in the other measured metabolites (lactate, pyruvate and urea). The local delivery of insulin did not affect the microcirculation of the lamellae (no changes in urea clearance). These results support the hypothesis of insulin modifying lamellar cellular metabolism by increasing glucose uptake and consumption. This metabolic shift may be relevant in terms of modifying the stability of the cytoskeleton of the epidermal basal cells (EBCs) and the organization of lamellar tissue.
doi:10.14264/uql.2015.873 fatcat:lhv5beb6mfaejnw7ez4mwdkzzu