REGULATION OF SKELETAL-MUSCLE CARBOHYDRATE OXIDATION DURING STEADY-STATE CONTRACTION

Pyruvate dehydrogenase complex (PDC) activation status has been descri bed as being central in the regulation of tissue substrate oxidation a s outlined by the glucose fatty-acid cycle. In the present study we ex amined the effects of reduced lipolysis, with use of nicotinate, and i ncreased PDC activation, with use of dichloroacetate (DCA), on substra te utilization during 20 min of submaximal steady-state contraction (s imilar to 80% of maximal O-2 uptake) in canine gracilis skeletal muscl e. At rest, PDC activation was unchanged by nicotinate but was similar to 2.5-fold higher in the DCA group than in the control group (P < 0. 05). During contraction, PDC activation status increased to 3.5 mmol a cetyl-CoA.min(-1).kg(-1) at 37 degrees C in the control group, remaine d at 4.5 mmol acetyl-CoA.min(-1).kg(-1) at 37 degrees C in the DCA gro up, but only increased to 2.2 mmol acetyl-CoA.min(-1).kg(-1) at 37 deg rees C in the nicotinate group (P < 0.05). However, the estimated amou nt of carbohydrate oxidized during the 20-min contraction was similar across groups and did not follow the degree of PDC activation (81.2 +/ - 22.9, 95.9 +/- 11.7, and 89.3 +/- 18.9 mmol glucosyl units/kg dry mu scle for control, nicotinate, and DCA, respectively). Thus it would ap pear that, during steady-state contraction, PDC activation status does not determine the rate of carbohydrate oxidation in skeletal muscle.