Erythrocyte Membrane Electron Transfer, Oxidative Stress, Body Mass and Lifestyle in Healthy and in Type 1 Diabetic Families

Erythrocytes export electrons across the cell membrane to external oxidants (such as ferryicyanide) through a redox system that remains still unknown. The rate of ferricyanide reduction varies as a function of cytoplasmic electron donor concentration. Indeed, the pathway is linked to a set of intracellular redox couples including NADH/NAD+, GSSG/SGSH, and ascorbate/vitamin C. Since the activity of membrane electron transport systems appears to be closely related to the redox homeostasis and the metabolic state of the cell, our aim was to characterise the membrane reducing system in healthy and in type 1 diabetes (T1DM) families and its relationship with nutritional indicators and oxidative biomarkers. Particularly, present research work aimed at evaluating in healthy and T1DM families: (a) the rate of erythrocyte electron transport in relation with body mass and metabolic efficiency, (b) modulating effects of diet and lifestyle on erythrocyte electron transfer system. We measured the erythrocyte electron transport to extracellular ferricyanide (RBC vfcy) in 100 healthy controls and 99 non-diabetic relatives of type 1 diabetics. Erythrocyte Na/H exchange (RBC NHE), RBC glutathione (GSH), plasma thiols, plasma and RBC malondialdheyde were also determined, in addition to plasma glucose, insulin, lipids, HbA1c, creatinine clearance, and urinary albumin. Moreover, we assessed dietary habits and lifestyle of 76 relatives and 95 healthy subjects by using the European Prospective Investigation of Cancer and Nutrition questionnaires. a. Among healthy controls, individuals with BMI≤25 kg/m2 had lower rates of electron transport in comparison with age-gender-matched subjects who were overweight or obese. Indeed, RBC vfcy correlated positively with two indices of fat body mass (BMI and circulating triglycerides), and negatively with an index of lean body mass (24-hour urinary creatinine excretion). Moreover, RBC vfcy showed a negative association with RBC NHE and plasma MDA. On the contrary, among relatives, RBC vfcy did not change significantly with BMI. It showed a positive association with RBC MDA, negative with RBC GSH. b. Both Spearman’s rank correlation and stepwise multiple regression analyses including lifestyle information found different independent variables to be positively associated with RBC vfcy: daily dietary intake of vitamin C among healthy controls, whereas time spent in regular exercise among relatives. In conclusion, (a) electron transfer catalysed by the transmembrane ferricyanide reductase activity may reflect the functional state of membrane proton pumps that modulate cellular metabolism by regulating the intracellular redox levels. In the case we should have a useful tool to indirectly evaluate some aspects of energy balance in human metabolic diseases by using easily accessible cells and simple laboratory procedure. Moreover, the transport system, that seems functionally normal, contributes to oxidation in T1DM families, whereas in healthy people it protects from oxidation. Furthermore, (b) dietary intake of vitamin C and sporting activities modulate erythrocyte electron transfer efficiency. In the cytosol, ascorbic acid or vitamin C can donate electrons to trans-plasma membrane electron transfer activity in erythrocytes. Thus, intracellular electron donors available from dietary sources can be very important in maintaining the redox environment of a cell, i.e. the summation of the products of the reduction potential and reducing capacity of the linked redox couples present. Our data also support indirect evidence suggesting that regular exercise may improve electron transport efficiency. However, the reason why independent lifestyle variables associated with RBC vfcy markedly differed among population subgroups remains unknown.