Inhibition of ubiquitin-activating enzyme E1 blocks ubiquitination of the key molecules of insulin signaling and prevents palmitate-inducible insulin resistance.226 UBC9 protein expression is decreased in muscle tissues from T2DM patients.227 Haploinsufficiency of UBC13 can ameliorate HFD-induced insulin resistance.228 Ubiquitin-conjugating enzyme E2O (UBE2O) is significantly upregulated in obese individuals with T2DM.229. This evidence concerns the gene INS and type 2 diabetes mellitus.