Fig. 5: OCN requires GPRC6A and IGF1R for the activation of the downstream insulin signaling pathway.
From: Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin
a, b OCN promoted insulin signaling in skeletal muscle (a) and liver (b). Ins, insulin. c–f OCN was associated with IGF1R (c, d) and IR (e), and GPRC6A was associated with IGF1R (f) in HEK 293 cells. g OCN was in the complex with endogenous IR and IGF1R in primary hepatocytes. h IGF1R was required for OCN-induced phosphorylation of insulin signaling mediators in primary hepatocytes. i IGF1R knockdown inhibited OCN-promoted 2DG uptake. C2C12 cells were transfected with IGF1R siRNAs and then treated with OCN or insulin for 2 h. n = 3 for three independent repeats of each experiment. j GPRC6A knockdown inhibited OCN-induced phosphorylation of insulin signaling mediators in primary hepatocytes. n = 3 (i, ctrl, Insulin), 6 (i, OCN). Data are presented as mean ± SEM. Analysis was two-way ANOVA followed by Fisher’s LSD multiple comparison test (i).
