Effects of metformin on endothelial glycocalyx properties in db/db mice

Recent studies show impaired glycocalyx properties during hyperglycemic conditions (1,2). The current aim was to determine the effects of the popular anti–diabetic drug metformin on glycocalyx properties. Db/db mice, 6–8 wks of age, were treated with metformin in their drinking‐water for 2 wks (MET, n=5); non‐treated db/db mice served as control (CON, n=5). At the experimental day, mice were infused with FITC–labeled 70 kDa dextrans (D70) and Texas Red‐labeled 40 kDa dextrans (D40), blood samples collected for 30 min, and plasma dextran concentrations determined using a spectrophotometer (2). Systemic glycocalyx D70 excluding volume was determined from the difference in initial distribution volume of D40 versus D70 (2,3), and was 0.009 ± 0.030 ml in CON and increased to 0.183 ± 0.057 ml in MET (p<0.05). The ratio of D70 to D40 clearance, reflecting glycocalyx barrier properties (2,3), was 0.619 ± 0.026 in CON and decreased to 0.530 ± 0.026 in MET (p<0.05). Dry to wet weight ratio, measured in heart and kidney, was 0.286 ±0.006 in CON and decreased to 0.257±0.009 in MET (p<0.05). Fasting blood glucose level was not changed in MET. These data show that MET treatment in db/db mice results in improved glycocalyx properties, irrespective of a change in fasting glucose. The glycocalyx improvement might underlie the observed restoration of organ fluid balance by metformin. Supported by Established Investigatorship from Netherlands Heart Foundation (2005T037) and Dutch Diabetes Research Foundation (2006.00.027)