Our findings warrant future studies to identify the cellular receptor for ApoA-IV in adipocytes, possible links between the ApoA-IV-NR1D1/NR4A1 pathway and PI3K-Akt signaling pathways, and the downstream targets of PI3K-Akt mediated signal transduction that underlie the upregulation of GLUT4 translocation and glucose uptake in adipocytes to assess their potential value as therapeutic targets for the treatment of IR and T2DM. Here, NR1D1 is linked to type 2 diabetes mellitus.