NOX4 and diabetes mellitus: 2014). Nox4 is constitutively active (Montezano et al. 2011), suggesting that its tissue level may reflect its activity. Nox4 has been identified as an upstream positive regulator of Nrf2 (Brewer et al. 2011; Schröder et al. 2012; Smyrnias et al. 2015). This study demonstrates that summer and diabetes, in parallel with cardiac and renal Nox4 downregulation, resulted in Nrf2 suppression in these organs (Fig. 3, Table 2).