Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets

Figure 3

Metformin-mediated activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) through the AXIN/LKB1-v-ATPase-Ragulator pathway. The lysosomal v-ATPase-Ragulator complex serves as an initiating sensor for switching between AMPK and mechanistic target of rapamycin (mTOR) activation. Metformin can directly act on v-ATPase and promote the translocation of AXIN/LKB1 onto the lysosomal surface to form a complex with v-ATPase-Ragulator, thus leading to AMPK activation and the simultaneous dissociation of Raptor and mTOR, which results in the suppression of mTOR complex 1 (mTORC1) [111].