In a study of cerebral vascular function in the animals used in the present study to assess tibial blood flow, NOS‐dependent vasodilation was reduced, whereas endothelin‐1 (ET‐1)‐mediated vasoconstriction was increased in isolated cerebral arteries of diabetic O‐T2D animals.59 These observations are consistent with our hypothesis that the T2D‐associated reduction in insulin‐stimulated bone blood flow is due to altered insulin vasodilatory response in the vascular endothelium of T2D animals. This evidence concerns the gene INS and type 2 diabetes mellitus.