Prolonged hyperinsulinemia increases the production of inflammatory cytokines in equine digital lamellae but not in striated muscle.
Authors: Jayathilake W M N K, de Laat M A, Furr M, Risco C, Lacombe V A
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary Equine metabolic syndrome (EMS) and its most serious complication, hyperinsulinemia-associated laminitis (HAL), remain poorly understood at the molecular level, yet this research provides crucial insight into the tissue-specific inflammatory cascade that precedes clinical disease. Jayathilake and colleagues induced prolonged hyperinsulaemia in healthy Standardbred horses via a 48-hour euglycemic-hyperinsulaemic clamp protocol, collecting tissue biopsies from digital lamellae, skeletal muscle and cardiac muscle to quantify inflammatory protein expression using Western blotting. Digital lamellar tissue showed marked upregulation of inflammatory cytokines (notably interleukin-1β) alongside acute phase proteins including heat shock protein 90, alpha-2 macroglobulin and fibrinogen—critically, *all* hyperinsulaemic horses developed clinically apparent laminitis within this timeframe, regardless of their metabolic status at enrolment. In stark contrast, inflammatory and acute phase protein expression remained unchanged in both skeletal and cardiac muscle, suggesting these insulin-sensitive tissues possess inherent protective mechanisms absent in the digital lamellae. These findings establish a differential inflammatory response that could guide development of tissue-targeted therapeutics and novel biomarkers for early detection, whilst highlighting why systemic approaches to EMS management may require lamellae-specific interventions to prevent the irreversible tissue damage characteristic of endocrinopathic laminitis.
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Practical Takeaways
- •Hyperinsulinemia alone is sufficient to trigger laminitis in previously healthy horses, making insulin management critical for laminitis prevention in EMS cases
- •Digital lamellae appear to be uniquely vulnerable to hyperinsulinemia-induced inflammation, suggesting tissue-specific pathophysiology that may guide future treatment strategies
- •The selective inflammatory response in lamellae but not muscle tissue points to localized mechanisms in laminitis development, potentially opening new avenues for targeted therapeutic intervention
Key Findings
- •All horses subjected to 48-hour prolonged euglycemic-hyperinsulinemic clamp developed laminitis regardless of previous health status
- •Digital lamellae showed significant upregulation of HSP90, A2M, fibrinogen, and interleukin-1β following prolonged hyperinsulinemia (P<0.05)
- •Skeletal and cardiac muscle showed no significant changes in inflammatory cytokine or acute phase protein expression despite hyperinsulinemia
- •Inflammatory cytokine upregulation in digital lamellae may serve as biomarkers and therapeutic targets for endocrinopathic laminitis