Our results suggest that reductions in LRRC8A signaling may contribute to impaired vascular function observed in humans in response to insulin and/or shear stress in the setting of obesity (Arcaro et al., 1999; Tack et al., 1998; Westerbacka et al., 1999; Williams et al., 2006) and insulin resistance (Murphy et al., 2007). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.