Vasodilator Response to Local Hyperinsulinemia

To the Editor: Cardillo et al recently reported that systemic but not local hyperinsulinemia causes nitric oxide (NO)-dependent vasodilatation.1 They suggest that mechanisms stimulated only by systemic but not local hyperinsulinemia contribute to insulin-mediated vasodilatation. We believe that this conclusion is mistaken.The changes in forearm blood flow during systemic and local hyperinsulinemia in their study were not directly comparable. Thus, although similar concentrations of insulin were achieved in both protocols, there was an artificial dissociation of insulin and glucose levels in the experiment with local hyperinsulinemia: in other words, no glucose supplement was administered in the local experiment, whereas euglycemia was maintained in the systemic study (using the clamp technique). It is likely, therefore, that glucose levels fell in the infused arm in the local experiment and that a discrepancy in forearm glucose uptake between the two conditions may have accounted for the different vasodilator responses to insulin observed.In support of this alternative explanation, we have consistently shown that intra-arterial infusion of insulin at 5 mU/min (resulting in insulin concentrations of 100 μU/mL …