IRS1 and Insulin resistance: Ectopic lipid accumulation triggers lipotoxicity, which is characterized by the release of FFAs and proinflammatory cytokines that impair insulin signaling by phosphorylating IRS-1 at serine residues; this leads to insulin resistance, which is a primary driver of type 2 DM (Shen et al., 2019; Shen et al., 2018; Peng et al., 2012).