This study investigates how a 12-week Western diet (WD) consumption alters the expression of key T2D-related genes (Ins2, Glut2, Pdx1, MafA, Nkx2.2, MafB, GcG, Sox9, C-Myc, Ngn3, PPARγ, Hnf-1α, Lrp5, and Tcf7l2) across major metabolic tissues in male C57BL/6J mice, and the selection of these genes is justified in the following section. This evidence concerns the gene LRP5 and type 2 diabetes mellitus.