IRS1 and Insulin resistance: Similarly, cytokines like TNFα or IL-1β promote insulin resistance by inhibiting insulin receptor substrate-1 (IRS-1), which plays a role in transmitting signals from insulin to intracellular pathways, such as the phosphoinositide 3-kinase/protein kinase B (PI3k/Akt) and extracellular signal-regulated kinase/mitogen-activated protein kinase (Erk/MAPK) pathway, leading to a reduction in glucose uptake.