Metabolic Markers of Insulin Resistance in Feline Hypertrophied Myocardium. Insulin Resistance in Heart Failure

Abstract

Investigation of myocardial tissue concentration of ATP, glucose transporters 1 and 4, pyruvate dehydrogenase, hexokinase 2, insulin receptor and adropin proteins, determining metabolic changes and possible insulin resistance in feline myocardium with hypertrophic phenotype. This is the pilot study for metabolic markers determination. Eighteen cats were studied, divided into 3 groups: Without cardiac disease (n = 5), cats with hypertrophic cardiomyopathy (n = 8), cats with chronic kidney disease and secondary myocardial hypertrophy (n = 5). Animals in the study were diagnosed for the primary disease by standard methods and algorithms. Cats were euthanized due to the end-stage chronic kidney disease, refractory heart failure or by owners’ will. The myocardium samples were obtained immediately after death. Samples for the metabolic study were taken from the apical part of the left ventricular free wall and fixed in liquid nitrogen at once and were stored in -80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp. (USA), included: Total ATP, pyruvate dehydrogenase, hexokinase II, Adropin, insulin receptor, GLUT1 and GLUT4. In the group with HCM, we discovered that levels of ATP, pyruvate dehydrogenase and adropin were severely suppressed in comparison to healthy cats, while GLUT1 and GLUT4 did not change. The concentration of hexokinase 2 and insulin receptor proteins significantly increased. In the group of secondary myocardial hypertrophy, suppression of most studied proteins was admitted, except insulin receptor. In conclusion, we discovered metabolic remodeling and development of insulin resistance in observed diseases with hypertrophy phenotype. We observed depression of pivotal enzymes proteins, limiting energy restoration potency for cardio myocytes.