Glyburide modulates insulin-mediated locomotor response of confluent cell cultures to wounding

We determined whether the sulfonylurea glyburide could modify the insulin-induced locomotor response to wounding of bovine aortic, pulmonary artery endothelial, and gerbil fibroma cells. Serum-deprived cells were preincubated in medium containing glyburide (10(-4) M) or diluent, then exposed to insulin (10(-6) to 10(-12) M) at the time of wounding, after which the centrosomal-orientation and migratory responses of the cells bordering the experimental wound were monitored by immunofluorescence microscopy and time-lapse cinemicrophotography, respectively. Insulin (10(-6) M) stimulated the centrosomal-orientation and locomotor responses, resulting in the narrowing of the linear wound. Glyburide enhanced the effect of insulin on both parameters of the locomotor response and also sensitized the cells to a previously ineffective concentration of insulin (10(-12) M). The action of glyburide depended on a preincubation period of greater than or equal to 60 min and was blocked by cycloheximide and actinomycin D. The relevance of this novel action of glyburide to the impaired healing process observed in diabetic patients requires further study.