Although several SNPs have been identified in IRS1 genes, only the Gly to Arg972 substitution of IRS-1 (rs1801278 SNP) seems to represent a key independent determinant in the onset of insulin resistance in T2D patients, affecting the ability of insulin to activate the PI3K cascade that physiologically regulates glucose metabolism by promoting glycolysis and inhibiting gluconeogenesis in insulin-sensitive tissues [77,78,79]. The gene discussed is INS; the disease is type 2 diabetes mellitus.