EDN1 and Insulin resistance: However, in addition to the increased secretion of counter-regulatory hormones in DKA [89] several other perturbations are candidates for mediating pre-treatment hypertension: 1) insulin resistance and endothelial dysfunction; 2) the increased oxidative stress caused by hyperglycemia [90], [91]; 3) and the ability of acetoacetate to increase the expression of the vasoactive peptide ET1 from capillary endothelial cells [92].