IRS1 and Insulin resistance: In addition, TNF (and also TLR stimulation) can also stimulate the JUN N-terminal kinase (JNK) family of serine/threonine protein kinases [16], a mechanism that promotes insulin resistance [17], and also decrease of insulin sensitivity since endoplasmic reticulum (ER) stress leads to insulin receptor substrate 1 (IRS1) phosphorylation [18].