In patients with T2DM, circulating FFAs directly enter into the liver; increased levels of hepatic FFAs can thus induce IR in the liver and activate some serine kinases, such as c-Jun-N-terminal kinase, p38, and ERK (Bi et al., 2013; Gao et al., 2018), leading to dephosphorylation of insulin receptor and its substrate 1/2 (IRS-1/2), thereby inhibiting Akt activity (Nakamura et al., 2009a). This evidence concerns the gene IRS1 and type 2 diabetes mellitus.