Insulin-Stimulated Myocardial Glucose Uptake and the Relation to Perfusion and the Nitric Oxide System

Abstract

In skeletal muscle, insulin increases glucose uptake through endothelium-derived nitric oxide (EDNO)-dependent vasodilation. Insulin also enhances myocardial glucose uptake, but it is unknown whether vasodilation participates in the underlying mechanism. We studied whether insulin-stimulated myocardial glucose uptake (MGU) is associated with perfusion changes and whether MGU is EDNO dependent. Myocardial perfusion (MBF) and MGU were measured three times with positron emission tomography in 8 healthy volunteers (56 ± 6 years): (1) During a hyperinsulinemic euglycemic clamp (clamp), (2) during clamp and blockage of the nitric oxide synthesis by L-NMMA and (3) during clamp and nitric oxide stimulation with nitroglycerin. We measured MBF at rest before and during clamp utilizing ¹³N-ammonia and ¹⁸F-fluoro-deoxy-glucose as perfusion and glucose tracers, respectively. Hemodynamics were affected neither by insulin nor by L-NMMA. Nitroglycerin reduced rate-pressure product. Insulin did not affect MBF. L-NMMA reduced MBF (0.60 ± 0.15 vs. 0.66 ± 0.14 ml/g/min; p < 0.05), while MGU was unchanged. Nitroglycerin did not alter MBF, while MGU was reduced (0.44 ± 0.11 vs. 0.52 ± 0.13 µmol/g/min; p = 0.05). Insulin-stimulated MGU does not rely on a simultaneous increment of MBF. Myocardial glucose uptake can be stimulated even when MBF decreases, suggesting that autoregulation of MGU is preserved despite uncoupling of vascular autoregulation.