Insulin and membrane microviscosity of erythrocytes as risk factors for stroke.

Insulin and Membrane Microviscosity of Erythrocytes as Risk Factors for Stroke To the Editor: I read with great interest the comments by Dr Kernan and colleagues1 dealing with the insulin sensitivity in nondiabetic patients with a recent transient ischemic attack or ischemic stroke. The results of their presented study demonstrated that pioglitazone may be effective for improving insulin sensitivity with a concomitant decrease in fasting plasma insulin concentration in these patients. Kernan et al proposed that because the prevalence of impaired insulin sensitivity is high among patients with stroke, thiazolidinediones may improve the morbidity and mortality of this disease. In a study we presented earlier, a relationship between membrane fluidity of erythrocytes and plasma insulin was investigated in patients with essential hypertension by means of an electron paramagnetic resonance method.2 Membrane fluidity (the reciprocal value of membrane microviscosity) is a physicochemical feature of biomembranes that is an important factor in modulating cell rheologic behavior.3,4 The membrane fluidity of erythrocytes was significantly lower in patients with essential hypertension than in normotensive subjects. The plasma content of insulin while fasting was significantly greater in hypertensive patients than in normotensive subjects. In addition, it was demonstrated that the higher the plasma insulin level, the lower the membrane fluidity of erythrocytes, which might indicate that hyperinsulinemia might be a determinant of membrane fluidity of erythrocytes in essential hypertension. Barbagallo et al reported that insulin significantly elevated the intracellular calcium level of human erythrocytes in a doseand time-dependent manner.5 With regard to the interaction between calcium and membrane fluidity, it was observed that calcium strongly decreased membrane fluidity of erythrocytes and other cells.6 In an in vitro study, we showed that insulin alone and in combination with calcium decreased membrane fluidity of erythrocytes in essential hypertension.7 It is likely that the insulin-evoked decrease in membrane fluidity of erythrocytes may be partially mediated by the increased intracellular calcium content. If the deformability of erythrocytes may be highly dependent on the membrane fluidity,8 the reduction in membrane fluidity might cause a disturbance in blood rheologic behavior and microcirculation, which could, at least in part, contribute to the risk factors of vascular complications. In this context it can be speculated that the reduced plasma insulin level evoked by pioglitazone might restore the rheologic behavior of erythrocytes and microcirculation in patients with stroke. It is possible that the effect of pioglitazone could be beneficial for the protection against repeated attacks of stroke in patients with hyperinsulinemia.