Fig. 9. A role of the ApoJ → LRP2 signaling pathway in glucose homeostasis and insulin signaling.

Circulating ApoJ is dominantly produced by the liver. Liver-derived ApoJ then transports to skeletal muscle where it binds to its receptor LRP2 on the cell surface, leading to increased molecular interaction between LRP2 and IR. The complexes of LRP2 with the IR then undergo co-endocytosis, which is an essential step of insulin signaling in skeletal muscle. As a result, downstream signaling components activate, leading to enhanced glucose transport system activity. Thus, the ApoJ → LRP2 signaling pathway is central in regulation of glucose homeostasis and insulin signaling.