Chloroquine Stimulates Phosphorylation Of The Amp-Activated Protein Kinase (Ampk) And Akt

Prior research has shown that AMPK may be a target of ataxia telangiectasia mutated (ATM) and that activation of Akt by insulin may require ATM. Accordingly, we hypothesized that ATM activators would increase phosphorylation of AMPK, acetyl coenzyme A carboxylase (ACC, an AMPK substrate), and Akt in cultured muscle cells. C2C12 cells were differentiated into myotubes in DMEM containing 2% horse serum (differentiation medium). Myotubes were incubated in differentiation medium with 0 μM, 250 μM, or 500 μM chloroquine, an ATM activator, for 1 hour. Myotubes incubated in 250 μM and 500 μM chloroquine had two‐ and three‐fold more phosphorylated AMPK (P‐AMPK), respectively, than control cells (P<0.05 and P<0.001, respectively). Consistent with its effect to increase P‐AMPK, 500 μM chloroquine also caused better than a two fold increase in P‐ACC (P<0.01). Additionally, myotubes incubated with 500 μM chloroquine had a two‐fold increase in P‐Akt at serine 473 (P<0.05). Another putative ATM activator, indole‐3‐carbinol, had no affect on AMPK phosphorylation. The chloroquine‐stimulated increase in P‐AMPK, P‐ACC, and P‐Akt may be relevant to previously reported hypoglycemic effects of chloroquine.