Metformin exposure affects human and mouse fetal testicular cells

International audienceMetformin exposure affects human and mouse fetal testicular cells used for reproductive abnormalities associated with insulin resistance (Diamanti-Kandarakis et al., 2010). Although the molecular mechanisms involved in metformin activity are not completely understood, it has been reported that metformin is transported into cells by organic cation transporters and could inhibit the respiratory complex I and/or activate the energy sensor AMP-activated protein kinase (AMPK) as described in hepatocytes and muscle (Zhou et al., 2001; Vander Heiden, 2011). Modifications to mitochondrial coupling and the cellular energy state (ATP/AMP ratio) induced by metformin could, at least in part, activate AMPK, switching off the anabolic process, and could be an explanation for its pleiotropic actions. However, different studies have demonstrated that metformin might act independently of AMPK, considering a direct regulation of the gluconeogenesis flux or a short-term inhibition of the mammalian TOR complex 1 by metformin (Foretz et al., 2010; Kalender et al., 2010