IRS1 and diabetes mellitus: Endoplasmic reticulum stress, an important feature of diabetes, has also been shown to increase TRIB3 expression, thus promoting cell death in response to endoplasmic reticulum stress [43].TRIB3 impairs insulin metabolic signalling by increasing serine phosphorylation of insulin receptor substrate 1 (IRS-1), reducing activation of phosphatidylinositol 3-kinase (PI3K)/Akt [44], or directly inhibiting the phosphorylation of Akt [45, 46].