JN The Journal Nutrition | Insulin Resistance In Equies
+ Author Affiliations
Read entire article at: http://jn.nutrition.org/content/136/7/2094S.full
*Department of Animal and Poultry Science, Virginia Polytechnic and State University, Blacksburg, VA, 24061-0303 and †Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1
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.
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.
Insulin resistance was first implicated in the pathogenesis of laminitis in the 1980s using oral glucose and i.v. insulin tolerance tests (1,2).
These tests indicated relative glucose intolerance and resistance to exogenous insulin in ponies that had previously experienced laminitis, compared with ponies with no history of laminitis. Field and Jeffcott (3) proposed a mechanism of insulin resistance–mediated vasoconstriction in laminitis.
Since then, our understanding of insulin resistance in laminitis has improved, due largely to technological advances in measurement.
Advancements include the use of specific and quantitative techniques to characterize the dynamic glucose and insulin system and more convenient proxies that statistically predict specific quantitative parameters (4,5). Using such techniques can better define the roles of insulin signaling and insulin resistance in the development of equine laminitis.
Here we provide the background of insulin resistance and its assessment, present existing data connecting insulin resistance to equine laminitis, and discuss possible mechanisms.
Our goal is to promote a better understanding of the role of insulin resistance in the development of equine laminitis, ultimately to improve management to avoid the disease.
Definition Insulin resistance is a general term for the inability of a normal concentration of insulin to produce a normal response from target tissues (6). Insulin resistance is a characteristic of type 2 diabetes and is different from a reduction in insulin action due to reduced circulating insulin as occurs in type 1 diabetes.
Insulin signaling refers to the stimulation of a response by insulin.
Insulin resistance could pertain to a breakdown in insulin-signaling mediators prior to the insulin receptor, which reduce circulating insulin or downregulate insulin-receptors.
More commonly observed, however, are alterations in the postbinding signal transduction associated with decreased insulin receptor-autophosphorylation and decreased tyrosine kinase activity, resulting in decreased insulin-receptor substrate-1 phosphorylation and reduced activation of phosphatidylinositol 3-kinase (7–9).
In addition, disruption of intracellular glucose metabolism regulated by enzymes such as hexokinase and glycogen synthase could reduce insulin-mediated glucose uptake and storage (7–10). To distinguish receptor-level and intracellular inhibition of insulin action we adopted
2 terms: insulin sensitivity, which describes reduced insulin-mediated glucose transport into the cell, and insulin ineffectiveness, which describes a failure of insulin-facilitated intracellular glucose metabolism (11).