Erythrocyte-derived measures of membrane lipid composition in healthy men: associations with arachidonic acid at low to moderate but not high insulin sensitivity

The lipid composition of erythrocyte membranes was explored as a surrogate for that of skeletal muscle in investigations into the influence of membrane fatty acid composition on insulin sensitivity. In a preliminary study (study 1), erythrocyte and monocyte/platelet membrane fatty acid percentages were compared with those of muscle membrane in 10 otherwise healthy men undergoing orthopedic surgery. In a further study (study 2), relationships between erythrocyte membrane fatty acid concentrations and insulin sensitivity, S(I), measured using the intravenous glucose tolerance test (IVGTT), were evaluated in 30 asymptomatic men. In study 1, significant positive correlations were found between muscle and erythrocyte membrane fatty acid percentages for 16:0 saturated fatty acid (r = 0.92, P <.001), and for the 18:2n-6, 20:4n-6, 20:5n-3, and 22:5n-3 polyunsaturated fatty acids (PUFAs) (r = 0.67 to 0.83, P <.05 to.01). There were fewer and weaker associations between muscle and monocyte/platelet membrane fatty acid compositions. In study 2, highly insulin-sensitive individuals (n = 8) had significantly lower erythrocyte membrane fatty acid concentrations than those with low/normal S(I). Among those with low/normal S(I) (n = 22), S(I) correlated positively with erythrocyte membrane arachidonic acid concentration (r = 0.57, P <.01) and with total PUFAs (r = 0.46, P <.05). Indices of delta 6 and delta 5 desaturase activities were significantly higher and lower, respectively, in high compared with low/normal S(I) individuals. For a range of fatty acids, erythrocyte membrane fatty acid composition shows close associations with that of muscle membranes. Measurements in erythrocyte membranes support a role for membrane arachidonic acid content in the modulation of insulin sensitivity, specifically at low/normal insulin sensitivities.