Genetic deletion of thioredoxin-interacting protein (Txnip) in cells can increase protein ubiquitination of Xbp1, decrease gluconeogenesis and increase insulin sensitivity.234 An increased level of UBE2v1- and Lys63-ubiquitinated proteins was found in patients with T2DM, and the latter is involved in the pathological process of tubular damage in diabetic nephropathy.235. This evidence concerns the gene INS and type 2 diabetes mellitus.