HNF4A and type 2 diabetes mellitus: Generally, canonical Wnt cascades such as Wnt3a can stimulate insulin secretion and enhance the proliferation of β cell by activating β-catenin/TCF/LEF-mediated Cyclin D1 transcription.50 However, in T2D, most non-classical Wnt ligands such as Wnt4 and Wnt2a are highly upregulated,159 inhibiting Wnt3a and promoting β cell dysfunction.160 In addition, Wnt2b and TCF7L2, encoding an important transcription factor TCF4, are associated with the susceptibility of T2D among individuals with impaired glucose tolerance161 (Fig. 2g)