GSK3B and type 2 diabetes mellitus: In addition, several studies have shown that increased GSK3β activity is accompanied by decreased IRS1 protein abundance in T2D.14,15 In particular, it has been shown that in Chinese hamster ovary (CHO) cells, high glucose-induced activation of GSK3 facilitates the ubiquitination and degradation of IRS1.16 However, whether similar mechanism works in striated muscle and, if so, which E3 ligase mediates the ubiquitination of IRS1 is still unclear.