Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle

Hyperinsulinemia increases lactate release by various organs and tissues. W hereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle N a+-K+-ATPase is responsible for increased muscle lactate production. To tes t this hypothesis, we assessed muscle lactate release in healthy volunteers from the [C-13] lactate concentration in the effluent dialysates of microd ialysis probes inserted into the tibialis anterior muscles on both sides an d infused with solutions containing 5 mmol/l [U-C-13] glucose. On one side, the microdialysis probe was intermittently infused with the same solution additioned with 2.10(-5) M ouabain. In the basal state, [C-13] lactate conc entration in the dialysate was not affected by ouabain. During a euglycemic -hyperinsulinemic clamp, [C-13] lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely rev ersed by ouabain (56% inhibition compared with values in the dialysate coll ected from the contralateral probe). These data indicate that insulin stimu lates muscle lactate release by activating Na+-K+-ATPase in healthy humans.