Figure 10. Proposed model for glucose-stimulated insulin secretion via activation and membrane association of Rac1 and downstream activation of ERK1/2.
We propose that acute exposure of INS-1 832/13 cells to stimulatory glucose (20 mM) results in the activation and membrane association of Rac1. This results in the activation of downstream effectors including ERK1/2, culminating in insulin release from the pancreatic β-cell. Our findings suggest that EHT 1864, a selective inhibitor of Rac1 activation, disrupts this signaling mechanism, thereby attenuating GSIS (see section 4).