Hyperinsulinemia, hyperleptinemia, and nitric oxide in the regulation of membrane micoviscosity .

and Nitric Oxide in the Regulation of Membrane Micoviscosity To the Editor: We read with interest the article by Dr Piatti and colleagues1 dealing with the relationship between hyperinsulinemia, hyperleptinemia, and nitric oxide (NO) in patients with restenosis after coronary stenting. The results of their study demonstrated that among the stented patients, insulin and leptin levels were higher in those with restenosis than in those without restenosis. In addition, NO release during an oral glucose tolerance test was blunted in patients with restenosis. The authors proposed that insulin resistance and endothelial dysfunction were independent predictors of early restenosis after coronary stenting. There is evidence that insulin might actively participate in the regulation of membrane function. Sela et al2 demonstrated that polymorphonuclear leukocytes (PMN) in essential hypertension showed increased intracellular calcium content correlating positively with the individual’s blood pressure and plasma insulin. They proposed that because PMN priming may lead to oxidative stress and inflammation, intracellular calcium and insulin are involved in the pathogenesis of hypertension-induced vascular injury. In a study we presented earlier, a relationship between membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and insulin was investigated in essential hypertension by means of an electron paramagnetic resonance method. We demonstrated that the higher the plasma insulin level, the lower the membrane fluidity of erythrocytes. This might indicate that hyperinsulinemia is involved in the regulation of membrane fluidity of erythrocytes.3 In an in vitro study, we showed that insulin alone and in combination with calcium decreased the membrane fluidity of erythrocytes.4 The decreased membrane fluidity of erythrocytes might cause a disturbance in the blood rheologic behavior and the microcirculation, which could contribute, at least in part, to the pathophysiology of circulatory disorders. One hypothesis is that insulin might accelerate abnormalities in intracellular calcium metabolism and membrane function in blood cells such as PMN and erythrocytes, which could partially explain the vascular complications in subjects with hyperinsulinemia. On the other hand, it was demonstrated that leptin increased the membrane fluidity of erythrocytes and improved the rigidity of cell membranes via the NOand cGMP-dependent mechanism,5 suggesting that insulin and leptin may exert opposite effects on membrane microviscosity of erythrocytes. In this context, we speculate that hyperinsulinemia and insufficient leptin-induced NO production could coordinately modulate the membrane function in patients with restenosis. It would be necessary to assess more precisely the functional interactions between insulin and leptin in the regulation of membrane microviscosity and their contribution to the mechanism underlying restenosis after coronary stenting.