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Development of Strategies to Increase Peripheral Insulin Responsiveness in Dietary-induced Insulin Resistant Horses
B.P. Fitzgerald
Department of Veterinary Sciences
Project Description
Insulin resistance may be defined as reduced responsiveness of peripheral tissues to insulin mediated glucose uptake. To maintain physiological concentrations of glucose, or euglycemia, in an insulin resistant condition, pancreatic output of insulin by beta cells increases, resulting in elevated circulating concentrations of insulin. In humans, compensatory hyperinsulinemia eventually leads to failure of insulin secretion by the pancreas and the pathological condition of type 2 diabetes. This form of diabetes was once thought to occur primarily in aging adults, hence the alternative name of adult onset diabetes. Today, however, type 2 diabetes is recognized as a major disease condition that may affect all age groups. In the horse, insulin resistance has been associated with several pathological conditions, including the development of laminitis, osteochondrosis dissecans lesions (OCD) colic cushing's disease and hyperlipidemia. However, it is unknown as to whether insulin resistance is causal to the development of these pathologies. In addition, preliminary studies by our laboratory demonstrate that the estrous cycle in insulin resistant mares is characterized by prolonged interovulatory intervals, compared to lean, insulin sensitive mares.
Impact
It is now clear from work in this laboratory and that of others that adipose tissue produces inflammatory cyctokines and in turn, these factors contribute to the development of insulin resistance. A recent publication demonstrates that the maintenance of elevated circulating concentrations of insulin leads to the development of laminitis. Therefore, current and future therapies will focus on maintaining insulin at normal physiological values.
Publications
Vick, M.M., Adams, A.A., Murphy, B.A., Sessions, D.R., Horohov, D.W., Cook, R.F., Shelton, B.J., and Fitzgerald, B.P. (2007). Relationship Between Inflammatory Cytokines, Obesity, and Insulin Sensitivity in the Horse, Journal of Animal Science, first published on January 30, 2007 as doi:10.2527/jas.2006-673