Key result
Euglycemic insulin clamp shifted myocardial fuel usage from fat to carbohydrates, increasing glucose, lactate, and pyruvate uptake while abolishing free fatty acid extraction (P<0.001).
Why the study?
Does insulin alter myocardial substrate metabolism and hemodynamics in healthy humans?
Does insulin alter myocardial substrate metabolism and hemodynamics in healthy humans?
p-value: p=<0.001
In healthy humans, insulin directly shifts myocardial metabolism from fat to carbohydrate utilization without altering cardiac hemodynamics.
Insulin shifts healthy myocardial substrate use toward carbohydrates without hemodynamic effects; extends mechanistic data but leaves open translation to disease states.
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)
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Ferrannini et al. (1993) studied Healthy (n=6). Euglycemic insulin clamp vs. Fasting state (baseline) was evaluated on Myocardial fuel extraction and hemodynamics (p=<0.001). Euglycemic insulin clamp shifted myocardial fuel usage from fat to carbohydrates, increasing glucose, lactate, and pyruvate uptake while abolishing free fatty acid extraction (P<0.001).
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