Low-dose metformin and PEN2-dependent lysosomal AMPK activation: benefits outnumber side effects
Longlong Liu, Pradeep Kumar Patnana, Subbaiah Chary Nimmagadda
Abstract
Recent advances demonstrated numerous molecular mechanisms of metformin based on the dosage and duration, yet our understanding is limited. Using a photoactive metformin probe Ma et al. Owing to its pleiotropic modes of action, its role in other pathophysiological conditions including metabolic complications, cancer, cardiovascular diseases, inflammation, ageing, gut microbiota, neuroprotection and COVID-19 were reported. It is widely accepted that metformin inhibits mitochondrial complex I of the electron transport chain and results in a decrease in ATP synthesis stimulating AMPK, inhibiting hepatic gluconeogenesis, increasing insulin sensitivity in the liver and intensifying glucose absorption in the muscles. In addition, AMPK-independent role for metformin in cell proliferation, glycolysis and oxygen consumption rate, tumour suppression and blocking of important pathways as mTOR were reported.