Prior to the publication by Carvalho-Filho and co-workers [33], the postulated mechanisms for insulin resistance involved either increased phosphotyrosine phosphatase activity (effectively reduced tyrosine phosphorylation) or increased serine phosphorylation of IRS proteins [16,18], and only increased or preferential serine phosphorylation of IRS proteins had been linked to insulin resistance mediated by their degradation [35,36]. This evidence concerns the gene IARS1 and Insulin resistance.