Insulin resistance in equids: possible role in laminitis.

Abstract

Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and the somatotropic axis of growth. Insulin resistance alters insulin signaling by decreasing insulin action in certain resistant pathways while increasing insulin signaling in other unaffected pathways via compensatory hyperinsulinemia. In humans, altered insulin signaling is implicated in reduced glucose availability to insulin-sensitive cells, vasoconstriction and endothelial damage, and inflammatory response. Although no direct evidence exists for insulin's role in these mechanisms in the laminitic horse, changes in the glucose availability, vasculature, and inflammation were all demonstrated in hoof separation. Insulin resistance was first implicated in the pathogenesis of laminitis in the 1980s using tolerance tests. Our present findings provide the first specific evidence of insulin resistance as a major predisposing condition for laminitis. Specific quantitative characterization of insulin resistance is essential toward identifying the following: 1) ponies in need of special management to avoid laminitis, and 2) potential management strategies to avoid laminitis by increasing insulin sensitivity, including reducing obesity, increasing exercise, and moderating dietary carbohydrates, particularly starch.