FIGURE 8.

Proposed mechanism for the effect of apoA-IV on glucose homeostasis through NR1D1. ApoA-IV synthesis and secretion by the small intestine is markedly stimulated by meal feeding. Any exogenously administered apoA-IV, as well as those released from the intestine, enter the circulation and are taken up by the hepatocytes. In hepatocytes, apoA-IV binds to NR1D1, activates NR1D1 to suppress the expression of gluconeogenic genes, and increases NR1D1 expression to further suppress gluconeogenesis. These actions of apoA-IV result in the decrease of glucose output from liver and the decrease of blood glucose.