Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle.
Hyperinsulinemia increases lactate release by various organs and tissues. Whereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle Na+-K+-ATPase is responsible for increased muscle lactate production. To test this hypothesis, we assessed muscle lactate release in healthy volunteers from the [13C]lactate concentration in the effluent dialysates of microdialysis probes inserted into the tibialis anterior muscles on both sides and infused with solutions containing 5 mmol/l [U-13C]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, [13C]lactate concentration in the dialysate was not affected by ouabain. During a euglycemic-hyperinsulinemic clamp, [13C]lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely reversed by ouabain (56% inhibition compared with values in the dialysate collected from the contralateral probe). These data indicate that insulin stimulates muscle lactate release by activating Na+-K+-ATPase in healthy humans.
Novel-Chaté
V
V
Institute of Physiology, Medical School, University of Lausanne, 7 rue du Bugnon, 1005 Lausanne, Switzerland.
Rey
V
V
Chioléro
R
R
Schneiter
P
P
Leverve
X
X
Jéquier
E
E
Tappy
L
L
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D019344:Lactic Acid / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D013997:Time Factors
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D019344:Lactic Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase