Sex‐specific endothelial cell response to insulin

Abstract

We have observed that following acute exposure to insulin, permeability of mesenteric microvessels to albumin (Ps) differs by sex (S Bingaman et al., FASEB J20 406.7 2006; R Sasaki et al., FASEB J20 205.3 2006).Occupancy of the endothelial cell (EC) insulin receptor leads to the activation of 2 pathways that generate the vasodilator nitric oxide on the one hand and the vasoconstrictor endothelin‐1 on the other. Given our working hypothesis that agents that are vasodilators elevate Ps, and agents that are vasoconstrictors reduce Ps, we posited that the sex‐specific responses to insulin result from sex differences in the contributions of the 2 pathways.To evaluate the cell signaling EC isolated from the mesenteries of adult male and female Sprague Dawley rats were grown in culture for up to 7 passages. Cell‐based ELISA was used to assess total and phosphorylated endothelial nitric oxide synthase (eNOS) and MAPK, and insulin receptor‐β (IRβ) expression after 30 minutes exposure to 10−7M Insulin as compared to its absence. Results were normalized against β‐tubulin expression for each group.IRβ expression was reduced only in EC from males, while both sexes showed differences in eNOS and MAPK expression and activity. These data demonstrate the capacity for vascular cells to retain and display sex‐differences in cell signaling in the absence of sex hormones.Support: HL093068, HCO6RR017353 & the MU Pulmonary/MPP Partnership