IRS2 and diabetes mellitus: Akt2 (which lays immediately downstream of IRS2 in the insulin signaling cascade) has been shown to control beta-cell growth and survival as well; it distinctively regulates glucose metabolism as Akt2-null mice develop severe diabetes with high loss of beta-cell mass, a phenotype clearly similar to the one observed with Irs2-null mice [28], [29], [53].