Insulin-stimulated myocardial glucose uptake and the relation to perfusion and the nitric oxide system.
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 (13)N-ammonia and (18)F-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 micromol/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.
Søndergaard
Hanne M
HM
Department of Cardiology B, Aarhus University Hospital (SKS), Aarhus, Denmark.
Bøttcher
Morten
M
Schmitz
Ole
O
Nielsen
Torsten Toftegaard
TT
Bøtker
Hans Erik
HE
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005996:Nitroglycerin