Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog

Abstract

In vivo small doses of insulin inhibit lipolysis, lower plasma FFA, and stimulate glucose disposal. Lowering of plasma FFA, either in the absence of a change in insulin or during combined hyperglycemia and hyperinsulinemia, promotes glucose uptake by heart muscle in vivo. In the isolated perfused heart, large doses of insulin directly stimulate heart glucose uptake. To assess the effect of physiological elevations of plasma insulin upon myocardial glucose and FFA uptake in vivo independent of changes in plasma substrate concentration, we measured arterial and coronary sinus concentrations of glucose, lactate, and FFA, and coronary blood flow in conscious dogs during a 30 min basal and a 2 h experimental period employing three protocols: (a) euglycemic hyperinsulinemia (insulin clamp, n = 5), (b) euglycemic hyperinsulinemia with FFA replacement (n = 5), (c) hyperglycemic euinsulinemia (hyperglycemic clamp with somatostatin, n = 5). In group 1, hyperinsulinemia (insulin = 73 ± 13 μU/ml) stimulated heart glucose uptake (7.3 ± 4.4 vs. 28.2 ± 2.8 μmol/min, P < 0.002), lowered plasma FFA levels by 80% (P < 0.05), and decreased heart FFA uptake (28.4 ± 4 vs. 1.5 ± 0.9, P < 0.01). When the fall in plasma FFA was prevented by FFA infusion (group 2), hyperinsulinemia (86 ± 10 μU/ml) provoked a lesser (P < 0.05) stimulation of glucose uptake (Δ = 8.2 ± 4.2 μmol/min) than in group 1, and there was no significant change in FFA uptake (25.3 ± 16 vs. 16.5 ± 4). Hyperglycemia (plasma glucose = 186 ± 8 mg/100 ml) during somatostatin infusion resulted in only a small rise in plasma insulin (Δ = 12 ± 7 μU/ml), and although plasma FFA tended to decline, heart glucose uptake did not rise significantly (Δ = 5.5 ± 3.2 μmol/min, P = NS). There was no significant change in coronary blood flow during any of the three study protocols. We conclude that, in the dog, insulin at physiologic concentrations: (a) stimulates heart glucose uptake, both directly and by suppressing the plasma FFA concentration, and (b) does not alter coronary blood flow. Hyperglycemia per se has little effect on heart glucose uptake.