Using micro‐PIV to assess the role of insulin and free radical scavenger therapies in treating the effects of chronic hyperglycemia on the microvascular glycocalyx of NOD mice

Abstract

The existence of a hydrodynamically relevant endothelial surface layer (ESL), ~ 0.5 μm thick in microvessels of wild‐type mouse, is well established under normal physiological conditions. Since nearly all chronic complications of diabetes are derived from vascular disease arising from hyperglycemia, and since the ESL is situated as the first line of defense against vascular damage, we seek to establish the effects of hyperglycemia on the ESL. We applied microviscometric analysis to data obtained using micro‐particle image velocimetry in cremaster‐muscle venules (20–60 μm diameter) of chronically hyperglycemic NOD mice. In mice without treatment, we observed that the ESL thickness is degraded to ~ 0.15 μm (n=20), compared with ~ 0.53 μm (n=23) in healthy wild‐type mice. This represents a significant degradation of the ESL (p<0.05), comparable to that seen after free‐radical damage due to light‐dye treatment. In mice treated with insulin therapy (0.3 u/d LinBit implant) the ESL thickness is degraded to ~ 0.18 μm (n=5). This result is not significantly different from the untreated group. In mice treated with synthetic catalytic free radical scavengers (EUK‐207, Proteome Systems, Ltd.) in addition to insulin therapy, the ESL thickness is ~ 0.49 μm (n=5). This is significantly thicker than that found in either of the chronically hyperglycemic groups (p<0.05) and not significantly different from the control group.