Background/Aims: The exact mechanism that links insulin resistance and vascular disease remains unknown. A significantly increased Na+-H+ exchanger (NHE 1) activity and a different effect of insulin on obese individuals erythrocyte NHE 1 has been suggested. These observetions may provide a link between obesity, hyperinsulinemia and vascular disease. Methods: The intracellular pH and sodium influx were measured before and after addition of insulin in erythrocyte suspensions from normal and obese individuals. Amiloride, a specific NHE 1 inhibitor, and staurosporine a protein kinase C inhibitor were used to inhibit erythrocyte NHE Results: Erythrocytes from normal individuals showed increased pH and increased sodium influx after insulin stimulation. This effect of insulin was inhibited by amiloride and by staurosporine as well. In contrast insulin had no effect on NHE 1 activity of erythrocytes from obese individuals. Conclusion: These ex vivo data indicate that erythrocyte NHE 1 activity in obese individuals is "insulin resistant". Erythrocytes may provide a simple system for the study of insulin resistance pathways in obesity..

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