IRS1 and obesity due to melanocortin 4 receptor deficiency: Inhibition of PTP1B was shown to have anti‐diabetic effects by improving insulin and leptin signalling in a model of diet‐induced obesity.86 Furthermore, knocking down PTP1B activates the PI3K pathway and protects podocytes from endoplasmic reticulum (ER) stress, which associates with podocyte apoptosis and proteinuria in DKD.87 Activated insulin receptor phosphorylates its downstream mediators insulin receptor substrates 1 and 2 (IRS1, IRS2).