Calcium influx: A possible role for insulin modulation of intracellular distribution and activity of 6-phosphofructo-1-kinase in human erythrocytes

Human erythrocyte cells contain specific, active insulin receptor. However, the physiological relevance of this receptor is unclear. Here we show that Ca2+ influx is 4-fold higher in erythrocytes upon insulin stimulation. These effects are dose-dependent and are diminished by insulin concentrations of 150 nM and higher. The insulin-stimulated Ca2+ influx depends on a tyrosine-kinase activity and involves the verapamil-dependent Ca2+ channels. Elevated intracellular Ca2+, in association with the Ca2+-binding protein, calmodulin, stimulates erythrocytes 6-phosphofructo-1-kinase activity. This activation involves the detachment of the enzyme from erythrocyte membranes, which has been described as an important mechanism of glycolysis regulation on these cells. Altogether, these results support evidence that insulin may increases glucose consumption in human erythrocytes, through a mechanism involving Ca2+ influx, calmodulin and the detachment of 6-phosphofructo-1-kinase from the erythrocyte membrane. (c) 2005 Elsevier Inc. All rights reserved.