Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin

We determined the effect of insulin on the fate of glucose and contractile function in isolated working hypertrophied hearts from rats with an aortic constriction (n = 27) and control hearts from sham-operated rats (n = 27). Insulin increased glycolysis and glycogen in control and hypertrophied hear ts. The change in glycogen was brought about by increased glycogen synthesi s and decreased glycogenolysis in both groups. However, the magnitude of ch ange in glycolysis, glycogen synthesis, and glycogenolysis caused by insuli n was lower in hypertrophied hearts than in control hearts. Insulin also in creased glucose oxidation and contractile function in control hearts but no t in hypertrophied hearts. Protein content of glucose transporters, protein kinase B, and phosphatidylinositol 3-kinase was not different between the two groups. Thus hypertrophied hearts are less responsive to the metabolic and functional effects of insulin. The reduced responsiveness involves mult iple aspects of glucose metabolism, including glycolysis, glucose oxidation , and glycogen metabolism. The absence of changes in content of key regulat ory molecules indicates that other sites, pathways, or factors regulating g lucose utilization are responsible for these findings.