In conclusion, this study for the first time explores the role of β-arrestins in DN and provides direct evidence that β-arrestin-1 and β-arrestin-2 share common mechanisms to mediate podocyte autophagy by negative regulation of ATG12–ATG5 conjugation, indicating that β-arrestins are critical components of multiple signal transduction pathways that link renal injury to reduced autophagy in DN. Here, ATG5 is linked to liver dysplastic nodule.