INS and Insulin resistance: Similar to what happens with GLUT4, insulin signaling increases membrane expression of IRAP which then leads to the proteolytic cleavage of vasopressin.55, , –58 The IRAP knockout mice have increased circulating vasopressin levels, insulin resistance, and persistent urinary concentration.56,59 Whether there is a direct link between IRAP, insulin resistance, high blood vasopressin levels, and cardiovascular disease is still unknown.