Decreased fluidity of isolated erythrocyte membranes in type 1 and type 2 diabetes. The effect of resorcylidene aminoguanidine.
Changes in the physico-chemical properties of erythrocyte membranes induced by nonenzymatic glycation as well as the possible prevention of their rise were studied. Using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), fluorescence anisotropy values were determined in erythrocyte membranes isolated from type 1 and type 2 diabetic patients with and without complications. The mean anisotropy values for the groups of diabetic patients were significantly higher than those for the control group (p < 0.01). This indicated pathologically decreased fluidity in cell membranes in the diabetics regardless of the type of diabetes or the presence of complications. The fluorescence anisotropy positively correlated (p < 0.01) with clinical parameters, such as glycohaemoglobin and plasma cholesterol content, which are important for the monitoring of the compensation status of the diabetic patient. Our results support the suggestion that protein crosslinking and oxidative stress induced by nonenzymatic glycation contribute to changes in the physico-chemical properties of erythrocyte membranes. In vitro testing of a new potential drug resorcylidene aminoguanidine (RAG) showed its ability to increase significantly (p < 0.001), to various extent (p < 0.01), the fluidity of both diabetic and control erythrocyte membranes. Upon the administration of RAG, reduced fluorescence anisotropy values for the groups of diabetic patients approached the normal values obtained for the controls. This may play an important role in the improvement of impaired cell functions found in diabetes that are controlled by the cell membrane.
Waczulíkova
I
I
Department of Biophysics and Chemical Physics, Faculty of Mathematics, Physics, and Information, Comenius University, Bratislava, Slovakia. waczulikova@fmph.uniba.sk
Sikurová
L
L
Cársky
J
J
Strbová
L
L
Krahulec
B
B
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000502:physiology*; D005454:Fluorescence Polarization; D006442:Glycated Hemoglobin / Q000032:analysis; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D006146:Guanidines; D008074:Lipoproteins; D014280:Triglycerides; C115168:resorcylidene aminoguanidine