Review Volume 12, Issue 9 pp 8742—8759

Figure 3. Metformin/2-deoxyglucose cotreatment delays ADPKD progression. Metformin interferes with ADPKD cell proliferation by inhibiting CFTR and mTOR signaling via AMPK 2-DG inhibits mTOR via two pathways: by suppressing ERK, an upstream activator of mTOR, and by competitively inhibiting glycolysis, leading to energy imbalance and AMPK activation. This further inhibits CFTR and mTOR, thereby synergistically inhibiting ADPKD proliferation. (2-DG, 2-deoxyglucose; CFTR, cystic fibrosis transmembrane conductance regulator; AMPK, AMP-activated protein kinase; mTOR, mechanistic target of rapamycin kinase; ERK: extracellular signal-regulated kinase; ADPKD, autosomal dominant polycystic kidney disease).