APPL1 and Insulin resistance: As one of the insulin-sensitizing fatty factors, APN is secreted by fat cells to improve insulin resistance and attenuate hyperglycemia as well as impair RANKL-stimulated RAW264.7 cells through its receptors as AdipoR1, AdipoR2 (Okada-Iwabu et al., 2013), and T-Cadherin (Denzel et al., 2010; Parker-Duffen et al., 2013) and its downstream factors of cohesive protein APPL1 (Mao et al., 2006).