SERPINE1 and Insulin resistance: Specifically, insulin resistance has been found to be associated with elevated plasma PAI-1 levels (Juhan-Vague and Alessi, 1997), and both proinsulin and insulin can stimulate PAI-1 expression (Sakamoto et al., 1999; Nordt et al., 2001), thus insulin-sensitizing agents such as metformin may have independent effects in decreasing PAI-1 levels in patients with type 2 diabetic (Ersoy et al., 2008).