Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.
Authors: Stokes Simon M, Bertin Francois R, Stefanovski Darko, Belknap James K, Medina-Torres Carlos E, Pollitt Christopher C, van Eps Andrew W
Journal: Equine veterinary journal
Summary
# Editorial Summary: Lamellar Energy Metabolism and Perfusion in Equine Endocrinopathic Laminitis Hyperinsulinaemia is implicated in endocrinopathic laminitis development, yet the precise pathophysiological mechanisms remain poorly understood. Researchers used microdialysis probes to directly sample the lamellae of eight horses during a 48-hour euglycaemic hyperinsulinaemic clamp procedure, measuring glucose, lactate, and pyruvate concentrations alongside tissue perfusion markers, with six control horses providing comparison data. Counter-intuitively, laminitis developed without lamellar hypoperfusion or signs of energy depletion; whilst lactate concentrations rose more steeply in hyperinsulinaemic horses compared to controls and pyruvate increased relatively, the lactate-to-pyruvate ratio failed to shift in the clamp group (suggesting maintained aerobic metabolism), and urea clearance—a proxy for perfusion—actually increased slightly in affected horses. These findings suggest that current therapeutic strategies targeting lamellar blood flow enhancement may not address the primary metabolic insult in hyperinsulinaemia-induced laminitis, implying that practitioners should look beyond perfusion deficits and consider alternative mechanisms such as direct toxic effects of insulin or altered cellular signalling pathways in the development of this devastating condition.
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Practical Takeaways
- •Current evidence suggests therapies focused on improving lamellar blood perfusion may not be effective in preventing endocrinopathic laminitis development, as laminitis occurred without perfusion deficits
- •Hyperinsulinaemia appears to alter lamellar energy metabolism (increased lactate and pyruvate) in ways that do not follow typical hypoxic/ischaemic patterns, suggesting different pathogenic mechanisms than traditionally assumed
- •Management of laminitis risk in hyperinsulinaemic horses should focus on metabolic control rather than strategies aimed at enhancing tissue perfusion
Key Findings
- •Lactate concentration increased significantly faster in hyperinsulinaemic horses during the clamp period compared to controls (P = 0.014)
- •Laminitis developed without evidence of lamellar hypoperfusion or energy stress, despite hyperinsulinaemia
- •Lamellar tissue perfusion (urea clearance) increased in hyperinsulinaemic horses relative to controls (P = 0.02)
- •Lactate-to-pyruvate ratio increased in control horses but not in hyperinsulinaemic horses during the clamp period