IRS1 and Insulin resistance: Growing evidence indicates that fetuin-A can modulate insulin-stimulated insulin receptor (INSR) and insulin receptor substrate 1 (IRS1) phosphorylation through the direct interaction with the insulin receptor β-subunit; moreover, fetuin-A is believed to strongly promote lipid-induced insulin resistance over the enhancement of free fatty acids binding to toll-like receptor 4 (TLR4).