Metformin can activate AMPK by different mechanisms, it can inhibit complex 1 of the mitochondrial respiratory chain causing in an increase in AMP levels which results in the activation of AMPK (El-Mir et al., 2000; Hawley et al., 2010; Owen et al., 2000) or Metformin can activate LKB1 (Garrido-Urbani et al., 2011; Rattan et al., 2011; Xie et al., 2008), a tumor suppressor kinase that is mutated in Peutz-Jeghers Syndrome (Hemminki et al., 1998), and an upstream regulator of SNRK and AMPK. This evidence concerns the gene PRKAA1 and Peutz-Jeghers syndrome.