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 relationshipsbetween this membrane property and insulin sensitivity are contrasting(3, 4, 5, 6). Recently we enrolled 28 obese subjects (13 men and 15 women; mean age, 38.18 ± 13.52 years; body mass index, 35.0 ± 5.6kg/m2), which included 11 subjects with normalglucose tolerance (NGT) and 17 subjects with type 2 diabetes (DM). Allsubjects were insulin resistant. This was demonstrated by employing aneuglycemic hyperinsulinemic clamp (7). In this group, theglucose disposal (M), calculated on the basis of the amount of glucoseinfused, was 1.45 ± 1.01 mg/kg per minute (range, 0 to 3.27 mg/kgper minute), whereas the glucose metabolic clearance rate (MCR), calculated by dividing the amount of glucose metabolized by the plasmaglucose concentration, was 1.67 ± 1.15 mL/kg per minute (range, 0to 3.80 mL/kg per minute). Leukocytes separated from fasting venousblood 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 wasexamined by labeling intact cells with the fluorescent probe1-[4-(trimethylamino) phenyl]-6-phenyl 1,3,5-hexatriene (TMA-DPH), which explores the superficial regions of the membrane, and calculatingthe fluorescence polarization degree, inversely related to the membranefluidity (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 reducedin comparison with normal subjects (normals, 0.338 ± 0.008; obeseNGT, 0.353 ± 0.007; obese with type 2 DM, 0.350 ± 0.012;p < 0.01). In normal patients, obese patientswith NGT, and obese patients with type 2 DM, no significant correlationwas found between PMN membrane fluidity and the following metabolicparameters: fasting blood glucose level, glycated hemoglobin, totalcholesterol, and triglyceride level. In obese patients with NGT, no correlation was observed between PMN membrane fluidity and theparameters (M and MCR) reflecting insulin resistance, whereas in obesepatients with type 2 DM, a significant negative relationship waspresent between PMN membrane fluidity and both of these clampparameters, showing that the decrease of PMN membrane fluiditycoincided with a reduction in the degree of insulin resistance. In a previous report (6), we observed a decrease of PMNmembrane fluidity in a group of subjects with insulin resistance (12obese subjects with normal or altered glucose tolerance and 7 type 2diabetic subjects without obesity), but we did not observe anyrelationship between PMN membrane fluidity and the two clampparameters, which reflected the degree of insulin resistance. Our present data confirm other studies that found, in obese subjectsand in type 2 diabetic subjects, a decrease in membrane fluidity oferythrocytes (5, 10) and platelets (11) andcontrast with those obtained by Tong et al. (4), who foundin type 2 diabetic subjects an increase of the MN leukocyte membranefluidity, using diphenylhexatriene, a fluorescent probe that exploresthe membrane lipid core (4). The same authors found apositive correlation between MN membrane fluidity and insulinresistance, similar to that observed by us, although in their study the MN membrane fluidity was increased. The statistical relationship between PMN membrane fluidity andinsulin resistance observed in obese subjects with type 2 DM isdifficult to explain from a biological point of view. We retain thatthe evaluation of membrane fluidity, carried out by employingfluorescence spectroscopy, is greatly influenced by the probe employed, and that the results obtained in small groups do not allow solidconclusions. Our data, concerning two small groups of obese subjects, arepreliminary, but recognizing the role of PMN membrane fluidity on PMNfunction and considering that PMN cells are mediators of vasculardamage (12), we believe that the study of the functionalaspects of these leukocytes is useful.