Figure 1.

Dual targeting of AMPK signaling by 1,25(OH)₂D₃ and metformin. Hypothesized mechanisms through which 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) influences the activity of AMP-activated protein kinase (AMPK) and hence cell survival are depicted by dashed lines and include: (1) Modulation of mitochondrial biogenesis/activity with the subsequent deregulation of energy status; (2) Induction of LKB1 expression/activity; (3) Disruption of non-mitochondrial energy-producing processes (e.g., cellular glucose uptake and glycolysis); (4) Direct AMPK activation via induction of AMPK expression or inhibition of inactivating phosphatase expression.