Polymorphonuclear Leukocyte Membrane Fluidity and Insulin Resistance in Obese Subjects

Abstract

Dear Sir:Although cell membrane fluidity influences insulin activity (1,2), the clinical data regarding the relationships between this membrane property and insulin sensitivity are contrasting (3-6).Recently we enrolled 28 obese subjects (13 men and 15 women; mean age, 38.18 Ϯ 13.52 years; body mass index, 35.0 Ϯ 5.6 kg/m 2 ), which included 11 subjects with normal glucose tolerance (NGT) and 17 subjects with type 2 diabetes (DM). All subjects were insulin resistant. This was demonstrated by employing an euglycemic hyperinsulinemic clamp (7). In this group, the glucose disposal (M), calculated on the basis of the amount of glucose infused, was 1.45 Ϯ 1.01 mg/kg per minute (range, 0 to 3.27 mg/kg per minute), whereas the glucose metabolic clearance rate (MCR), calculated by dividing the amount of glucose metabolized by the plasma glucose concentration, was 1.67 Ϯ 1.15 mL/kg per minute (range, 0 to 3.80 mL/kg per minute). Leukocytes separated from fasting venous blood were subdivided into mononuclear (MN) and polymorphonuclear (PMN) cells using a Ficoll-Hypaque medium (Histopaque-1077; Sigma Diagnostics, St. Louis, MO). The PMN membrane fluidity was examined by labeling intact cells with the fluorescent probe 1-[4-(trimethylamino) phenyl]-6-phenyl 1,3,5-hexatriene (TMA-DPH), which explores the superficial regions of the membrane, and calculating the fluorescence polarization degree, inversely related to the membrane fluidity (8,9). The measurement was taken at 37°C, using a spectrophotofluorimeter (Mod. LS5; Perkin-Elmer, Beaconsfield, UK).In obese subjects, the PMN membrane fluidity was significantly reduced in comparison with normal subjects (normals, 0.338 Ϯ 0.008; obese NGT, 0.353 Ϯ 0.007; obese with type 2 DM, 0.350 Ϯ 0.012; p Ͻ 0.01). In normal patients, obese patients with NGT, and obese patients with type 2 DM, no significant correlation was found between PMN membrane fluidity and the following metabolic parameters: fasting blood glucose level, glycated hemoglobin, total cholesterol, and triglyceride level. In obese patients with NGT, no correlation was observed between PMN membrane fluidity and the parameters (M and MCR) reflecting insulin resistance, whereas in obese patients with type 2 DM, a significant negative relationship was present between PMN membrane fluidity and both of these clamp parameters, showing that the decrease of PMN membrane fluidity coincided with a reduction in the degree of insulin resistance.In a previous report (6), we observed a decrease of PMN membrane fluidity in a group of subjects with insulin resistance (12 obese subjects with normal or altered glucose tolerance and 7 type 2 diabetic subjects without obesity), but we did not observe any relationship between PMN membrane fluidity and the two clamp parameters, which reflected the degree of insulin resistance.Our present data confirm other studies that found, in obese subjects and in type 2 diabetic subjects, a decrease in membrane fluidity of erythrocytes (5,10) and platelets (11) and contrast with those obtained by Tong et a...