Abstract 782: Chronic and Acute Metabolic Interventions Improve Cardiac Metabolism and Enhances Cardiac Efficiency and Ischemic Tolerance in Type 2 Diabetes
Hearts from type 2 diabetic db/db mice demonstrate reduced glucose oxidation (GLUox) and over-reliance on fatty acid oxidation (FAox) for energy production. Hearts from db/db mice also show ventricular dysfunction, as well as reduced resistance to ischemic injury. Determination of the relationship between ventricular pressure-volume area (PVA) and myocardial oxygen consumption (MVO2) in isolated perfused db/db hearts has reveal reduced cardiac efficiency in these hearts, as reflected by a significant decrease in unloaded MVO2 (y-intercept of the MVO2-PVA relationship). In the present study we show that both chronic (5 wks) treatment with the PPARγ ligand, rosiglitazone (RSG), as well as acute administration of high glucose (33 mmol/L) and insulin (900 μmol/mL) in the perfusion buffer (G+I) normalized cardiac metabolism, and reduced unloaded MVO2 in ex vivo perfused db/db hearts. Measurement of post-ischemic functional recovery in isolated hearts following low-flow ischemia was also found to be significantly improved both in hearts from RSG-treated mice and in G+I perfused db/db hearts. These results suggest that not only a chronic antidiabetic treatment, but also acute administration of glucose and insulin, cause a metabolic shift in favor of glucose, improve cardiac efficiency and enhance ischemic resistance in type 2 diabetic hearts.