The effects of hyperglycemia on the directed migration of wounded endothelial cell monolayers

To determine if cellular motility is affected by abnormal concentrations of ambient glucose, we utilized an endothelial cell monolayer model of wounding to observe the effect of hyperglycemia on the serum-mediated polarization and migration responses of cells at the edge of the wound. We found that hyperglycemia inhibited the rapid polarization response and the consequent cellular migration induced by 20% fetal bovine serum. The inhibitory effect of glucose was significant at a concentration of 11 mmol/L and became more pronounced at higher glucose concentrations. The effect of hyperglycemia on the two components of cell locomotion differed from the inhibitory action of mannitol, another hyperosmolar agent, in two ways (1) the glucose-induced inhibition persisted in cells reincubated in medium containing physiologic glucose (5.5 mmol/L); and (2) the inhibitory effect of glucose was blocked in cells preincubated in medium containing either the sulfonylurea glyburide, or D-myo-inositol. These observations may be relevant to the pathogenesis and management of accelerated atherosclerosis associated with the diabetic state.