The Effect of Insulin and FFA on Myocardial Glucose Uptake

Abstract

In addition to direct stimulation of glucose uptake and metabolism in cardiac myocytes, insulin inhibits lipolysis and, thereby, reduces serum free fatty acid (FFA) concentrations. This, in turn, has been suggested to enhance myocardial glucose utilization. To study the mechanism of insulin action on myocardial glucose uptake (MGU)in vivo, five patients with stable coronary artery disease were studied with positron emission tomography (PET) and [18F]FDG. All patients underwent two PET studies after a 12-h fast, once during low serum FFA but high insulin concentrations (during insulin clamp), and once during low serum FFA and low insulin concentrations (in the fasting state after two oral doses of 250 mg of an antilipolytic drug, acipimox). The MGU in the normal myocardium was measured using dynamic PET imaging. Plasma glucose concentrations were comparable during the insulin clamp and after administration of acipimox (5.0±0.4v5.2±0.3 mmol/l, n.s.). Serum insulin concentrations were high during clamp but remained in low fasting concentrations after acipimox (74±9 mU/lv6±5 mU/l,P=0.0001). Serum FFA concentrations were similar during both approaches (230±110v200±40μmol/l, respectively, n.s.). No difference in cardiac work load was detected between the approaches. The calculated MGU values in normal myocardium were similar during both approaches (57±23μmol/min/100 gv61±14μmol/min/100 g, respectively, n.s.). The MGU values correlated inversely to serum FFA concentration (r=−0.87,P=0.001) and directly to myocardial work load (r=0.73,P=0.016) but not to serum insulin concentration. Thus, when serum FFA concentrations are comparably suppressed by insulin or acipimox, the glucose uptake in the normal myocardium is similar in patients with coronary artery disease. Therefore, the effect of insulin on myocardial glucose uptakein vivois mainly mediated via inhibition of lipolysis.