Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans

Abstract

We quantitated how lowering of free fatty acid (FFA) by an antilipolytic agent (acipimox) in the fasting state changes glucose uptake in heart and skeletal muscles. Glucose uptake in these tissues was measured two times in seven normal subjects, once after acipimox and once after placebo, using positron emission tomography-derived [18F]fluoro-2-deoxy-D-glucose kinetics. Plasma glucose and insulin remained at their fasting concentrations in both studies. Fasting FFA concentrations were 60% lower after acipimox (238 +/- 39) than placebo (645 +/- 78 mumol/l, P < 0.001). Glucose uptake increased 6 +/- 2-fold in the heart by acipimox (344 +/- 49 vs. 108 +/- 40 mumol.kg muscle-1.min-1, P < 0.002) and 1.5-fold in arm muscles (27.7 +/- 2.6 vs. 18.6 +/- 1.2 mumol.kg muscle-1.min-1, P < 0.02). Heart (r = -0.93, P < 0.001) and arm (r = -0.82, P < 0.001) glucose uptakes were inversely related to serum FFA. We conclude that serum FFA are inversely related to glucose uptake in heart and arm skeletal muscles after an overnight fast. These data indicate that compensatory glycogenolysis, although it may occur, does not prevent operation of the glucose-FFA cycle under fasting conditions.