METABOLIC AND HEMODYNAMIC-EFFECTS OF INSULIN ON HUMAN HEARTS

Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta-hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure. In conclusion, physiological hyperinsulinemia 1) specifically enhances myocardial glucose, lactate, and pyruvate uptake; 2) converts cardiac fuel reliance from fat to carbohydrate (by suppressing lipolysis) with no change in oxygen consumption; and 3) does not affect cardiac hemodynamics and external work.