THE EFFECT OF INSULIN AND FFA ON MYOCARDIAL GLUCOSE-UPTAKE

In addition to direct stimulation of glucose uptake and metabolism in cardiac myocytes, insulin inhibits lipolysis and, thereby, reduces ser um free fatty acid (FFA) concentrations. This, in turn, has been sugge sted to enhance myocardial glucose utilization. To study the mechanism of insulin action on myocardial glucose uptake (MGU) in vivo, five pa tients with stable coronary artery disease were studied with positron emission tomography (PET) and [F-18]FDG. All patients underwent two PE T studies after a 12-h fast, once during low serum FFA but high insuli n concentrations (during insulin clamp), and once during low serum FFA and low insulin concentrations (in the fasting state after two oral d oses of 250 mg of an antilipolytic drug, acipimox). The MGU in the nor mal myocardium was measured using dynamic PET imaging. Plasma glucose concentrations were comparable during the insulin clamp and after admi nistration of acipimox (5.0 +/- 0.4 v 5.2 +/- 0.3 mmol/l, n.s.), Serum insulin concentrations were high during clamp but remained in low fas ting concentrations after acipimox (74 +/- 9 mU/l v 6 +/- 5 mU/l, P = 0.0001). Serum FFA concentrations were similar during both approaches (230 +/- 110 v 200 +/- 40 mu mol/l, respectively, n.s.). No difference in cardiac work load was detected between the approaches. The calcula ted MGU values in normal myocardium were similar during both approache s (57 +/- 23 mu mol/ min/100 g v 61 +/- 14 mu mol/min/100 g, respectiv ely, n.s.), The MGU values correlated inversely to serum FFA concentra tion (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 se rum FFA concentrations are comparably suppressed by insulin or acipimo x, the glucose uptake in the normal myocardium is similar in patients with coronary artery disease. Therefore, the effect of insulin on myoc ardial glucose uptake in vivo is mainly mediated via inhibition of lip olysis. (C) 1995 Academic Press Limited