FIGURE 7.
The model of Egr-1/GGPPS/Erk1/2 pathway regulating insulin resistance in hyperinsulinism. Egr-1 is greatly increased in hyperinsulinism and in insulin resistance through activation of the Erk1/2 MAPK pathway. The highly expressed Egr-1 can reactivate Erk1/2 by triggering GGPPS transcription and promoting Ras membrane association. Furthermore, the sustained activation of Erk1/2 can phosphorylate IRS-1 on Ser612 and inhibit its activity. Insulin resistance eventually results from impaired glucose uptake.