Gender differences in endothelial function in aortas from type 2 diabetic model mice.

Type 2 diabetes mellitus is associated with high mortality and morbidity, mainly due to coronary artery disease and atherosclerosis, although female gender is a protective factor in the development of, for example, atherosclerosis and hypertension. Our main aim was to investigate gender differences in endothelial function in aortas from type 2 diabetic model mice. The nonfasting plasma glucose level was significantly elevated in diabetic mice (both males and females). The plasma insulin level was not different between controls and diabetics (either gender). The plasma adiponectin level was decreased by diabetes, and was lower in males. In control aortas (from males or females), the clonidine-induced relaxation was abolished by Akt-inhibitor treatment. In diabetic males (versus both control males and diabetic females): a) the clonidine- and insulin-induced endothelium-dependent aortic relaxations were impaired, but the acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced aortic relaxations were not, b) the norepinephrine (NE)-induced aortic contractile response was enhanced, c) systemic blood pressure was elevated, and d) the clonidine-stimulated Ser-473 phosphorylation of Akt in the aorta was decreased. These results suggest that endothelial functions dependent on the Akt pathway are abrogated by type 2 diabetes only in male mice.