SummaryType 2 diabetic patients are known to frequently have a high insulin level and were recently described as having high plasminogen activator inhibitor (PAI) activity, compared to normal controls. As we have shown in several clinical conditions (normal subjects, obese patients, angina pectoris patients) that plasma PAI activity was linked with plasma insulin, we have studied in 38 type 2 diabetic patients the relationship between PAI activity, insulin and other parameters. Patients showed higher level of PAI activity, as well as plasma glucose, insulin, triglyceride, cholesterol and Apolipoprotein B levels than normal controls; highest values were observed with diabetic patients also affected by coronary artery disease. A significant correlation was found between PAI activity and insulin (r = 0.60, p <0.001), body mass index (r = 0.32, p <0.05) and Apolipoprotein B (r = 0.33, p <0.05). The two latter correlations disappeared after adjustment for insulin.These results are in agreement with our previous report showing an in vitro effect of insulin on the synthesis of PAI by a hepatocellular cell line. Hyperinsulinemia presented by type 2 diabetic patients may increase the hepatic synthesis of PAI, inducing an hypofibrinolysis, which could play a role in the development of the vascular complications.Attempts to reduce hyperinsulinemia could have a favorable effect by lowering PAI activity.
Summary. Filtrability of erythrocytes obtained from uncontrolled Type I (insulin-dependent) diabetic patients is abnormal, but is corrected by insulin added in vivo or in vitro. As erythrocyte filtrability depends on several determinants, we chose to study a membrane property of erythrocytes from diabetic subjects. Membrane fluidity was studied by fluorescence polarization using a lipophilic probe, the diphenyl-hexatriene and the Coulter Epics V together with a laser Spectra-physics 2000. Fluorescence polarization values obtained for 31 normal subjects (0.253 +0.043 SD) and 31 uncontrolled Type 1 diabetic patients (0.231 + 0.043 SD) were significantly different (p < 0.01). Insulin (2.5.10 -9 mol/1) added in vitro increased Given a relationship between the lipid bilayer and membrane cytoskeleton proteins, this insulin-correctable abnormality of erythrocyte membrane fluidity may be an important determinant of the rheological behaviour of erythrocytes from diabetic patients.Keywords: Membrane, fluorescence polarization, erythrocytes, diabetes, insulin.The erythrocytes &uncontrolled Type 1 (insulin-dependent) diabetic patients have abnormal rheological properties [1][2][3][4]. Modifications in the erythrocyte membrane could be the cause of these theological abnormalities. Biochemical abnormalities have been described [5][6][7] in the membrane, and change in its viscosity have been demonstrated by the fluorescence polarization technique [7][8][9] or electron spin resonance [10]. However, these results have been challenged [11].We have previously observed that the poor filtrability of erythrocytes from uncontrolled Type 1 diabetic patients was rapidly corrected by insulin added in vivo or in vitro [3,4].The aim of this study was therefore to verify whether insulin directly modified the membrane fluidity assessed by fluorescence polarization if such an abnormality was found in cells from diabetic patients. For this purpose, ghosts prepared from erythrocytes originating from uncontrolled Type 1 diabetic patients and matched controls were incubated with and without insulin. Fluorescence polarization was studied with a lipophilic probe, the 1,6 diphenyl-l,3,5 hexatriene (DPH).
Subjects and methodsThe subjects were 31 Type I (insulin-dependent) diabetic patients, 20 males and 11 females, aged 26 to 64 years (mean + SD = 44 _+ 16), uncontrolled at the time of the study. None of the patients were smokers, and women did not use oral contraceptive agents. Diabetes duration ranged from 1 to 26 years (mean + SD = 9.6 + 7 years). Two patients had macroproteinuria (i.e. > 500 mg/day) but serum creatinine did not exceed 100 btmol/l in any of the patients. Nine had background retinopathy at fundus examination after papillary dilatation. Patients with proliferative retinopathy or symptoms of cardiovascular disease were excluded from the study. Treatment consisted of two or three insulin injections per day except for two cases treated with one daily insulin injection. Glycosylated haemoglobin values, assessed by microchromatography at...
Erythrocytes from diabetic patients show abnormal rheology. Pentoxifylline, a methylxanthine, improves the abnormal deformability of diabetic erythrocytes, but its mechanism of action remains unclear. We have studied the effect of pentoxifylline on the lipid order of erythrocyte membranes from controls and patients with Type I diabetes. We studied the structural organization of membrane lipids in individual erythrocyte ghosts by fluorescence polarization using a cell sorter. Fluorescence polarization values (P) for 17 controls (P = 0.244) and 20 diabetic patients (P = 0.215) were significantly different. Pentoxifylline added in vitro had no effect on normal membranes, but significantly increased at 10(-5) mol X l-1 (P = 0.233), and normalized at 10(-4) mol X l-1 (P = 0.243), the P value of membrane ghosts from diabetics.
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