Prolonged hyperinsulinemia increases the production of inflammatory cytokines in equine digital lamellae but not in striated muscle.

The research investigates how persistent high levels of insulin affects different tissues in horses, specifically the tissue in the hooves and muscles, and identifies certain proteins that might be valuable markers or targets for managing and treating horse-specific metabolic syndrome and laminitis.

Research Context

• The research is grounded in understanding the impact of equine metabolic syndrome (EMS), particularly hyperinsulinemia-associated laminitis (HAL), a serious complication of EMS. These conditions are characterized by prolonged periods of high insulin in the body.
• Laminitis is an inflammation of the lamellar tissue found in horses’ hooves. It is a painful and potentially crippling condition that can ultimately lead to a horse needing to be euthanized.
• While it’s recognized that hyperinsulinemia is a critical condition in EMS and HAL, the explicit mechanisms and affected areas are not fully known.

Research Approach

• The research used healthy Standardbred horses as the subject of the study. Horses were either submitted to a prolonged euglycemic-hyperinsulinemic clamp (a methodology that maintains high insulin levels while keeping blood sugar normal) or served as a non-hyperinsulinemic control group.
• Biopsies were performed on the horses following a 48-hour period of either hyperinsulinemia or non-hyperinsulinemia. Tissue samples were taken from the digital lamellar (hoof) tissue and striated muscle tissue.

Key Findings

• All horses that were subjected to hyperinsulinemia developed laminitis, irrespective of their health status before the study.
• When examined, the expressions of certain proteins were found to be significantly increased in the lamellar tissues in the case of hyperinsulinemic horses.
• Proteins such as heat shock protein 90 (HSP90), alpha 2 macroglobulin (A2M), and fibrinogen (α, β isoforms), as well as certain inflammatory cytokines like interleukin-1β, were notably upregulated.
• In contrast, the expression of the inflammatory cytokines and proteins did not change in the heart and skeletal muscle tissues under the same conditions. This unexpected result may point to potential anti-inflammatory and heart-protective mechanisms that are activated in these specific tissues in response to hyperinsulinemia.

Research Implications

• The upregulation of these specific proteins in lamellar tissue during prolonged hyperinsulinemia could serve as potential biomarkers, helping to better diagnose and manage endocrinopathic laminitis in horses.
• Understanding the variation in cytokine and protein expression between different tissue types may also help develop new target-based therapies for equine metabolic syndrome and potentially uncover mechanisms that prevent inflammation and protect cardiac health.