Figure 6.

Lamtor1 attenuates insulin secretion by inhibiting the amplification pathways associated with glutamate and ACC1 metabolism. As demonstrated, a number of processes are required for Lamtor1 to produce this result, including: i) Inhibition of insulin secretion by reducing glutamate levels in whole cells and cytosol; ii) inhibition of incretin/cAMP signaling and prevention of cytosolic glutamate transport into insulin granules, thereby inhibiting insulin secretion (23); iii) promotion of AMPK and ACC1 phosphorylation, which leads to the inhibition of ACC1 activity and consequent decrease in insulin secretion (10). Lamtor1, late endosomal/lysosomal adaptor MAPK and mTOR activator 1; ACC1, acetyl-CoA carboxylase 1.