INS and cancer: Two major pathways are thought to account for the main actions of metformin and metformin's proposed anti-cancer effects (Figure 2); both pathways converge on mammalian target of rapamycin (mTOR): (1) AMPK (adenosine monophosphate-activated protein kinase) independent, driven by metformin's ability to secondarily lower serum insulin and (2) AMPK-dependent, regulated by metformin-suppression inhibition of mitochondrial complex-I (complex-I).