Whereas insulin enhances DAT activity (Knusel et al., 1990; Carvelli et al., 2002), hypoinsulinemia (produced by experimentally induced diabetes, insulin resistance, or fasting) reduces DAT activity (Owens et al., 2005; Williams et al., 2007; Sevak et al., 2008; Speed et al., 2011; Owens et al., 2012). This evidence concerns the gene INS and diabetes mellitus.