Metabolic and hemodynamic effects of insulin on human hearts

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

“…The fact that the heart can take up and oxidize large amounts of carbohydrate when deprived of FFA (20), together with the avid extraction of FFA from blood as shown in the present and previous studies, would suggest that circulating triglycerides are not an essential fuel for this tissue.…”

“…This is the case in spite of the fact that most myocardial ATP production is derived from FFA oxidation after an overnight fast (19). Although no data are available on myocardial metabolism during meal absorption, the heart readily switches to carbohydrate oxidation during infusion of insulin and glucose (20).…”

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

“…These results were obtained despite the fact that the metabolic evaluation was performed in patients subjected to hyperglycemia-hyperinsulinemia in an attempt to mimic postprandial metabolic conditions. It is well known that in normal subjects during this period the increase in insulin and glucose levels determines a shift toward the utilization of the glycolytic pathway (2,9). In addition, myocardial glucose utilization was positively correlated with cGMP (the second messenger of NOx) and maximal postischemia-induced hyperemic vasodilation while negatively correlated with TG and ET-1 levels.…”

The effects of insulin and short-term hyperglycaemia on myocardial blood flow in young men with uncomplicated Type I diabetes

“…In addition, the flow is directly dependent on blood pressure and modulated by mechanical forces in the myocardial wall [42]. At resting conditions it seems to take at least 2 h for physiological hyperinsulinaemia to induce significant vasodilation in myocardial vasculature [11,43]. However, in peripheral vasculature insulin, possibly by potentiating endothelium-dependent vasodilation, has been found to enhance the effect of endothelium-dependent vasodilators before any changes in basal blood flow can be detected [44,45].…”