Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction.
Pyruvate dehydrogenase complex (PDC) activation status has been described as being central in the regulation of tissue substrate oxidation as outlined by the glucose fatty-acid cycle. In the present study we examined the effects of reduced lipolysis, with use of nicotinate, and increased PDC activation, with use of dichloroacetate (DCA), on substrate utilization during 20 min of submaximal steady-state contraction (approximately 80% of maximal O2 uptake) in canine gracilis skeletal muscle. At rest, PDC activation was unchanged by nicotinate but was approximately 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 acetyl-CoA.min-1.kg-1 at 37 degrees C in the control group, remained at 4.5 mmol acetyl-CoA.min-1.kg-1 at 37 degrees C in the DCA group, but only increased to 2.2 mmol acetyl-CoA.min-1.kg-1 at 37 degrees C in the nicotinate group (P < 0.05). However, the estimated amount 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 muscle for control, nicotinate, and DCA, respectively). Thus it would appear that, during steady-state contraction, PDC activation status does not determine the rate of carbohydrate oxidation in skeletal muscle.
Timmons
J A
JA
School of Biomedical Sciences, University Medical School, Queen's Medical Center, Nottingham, United Kingdom. James_Timmons@sandwich.pfizer.com
Poucher
S M
SM
Constantin-Teodosiu
D
D
Macdonald
I A
IA
Greenhaff
P L
PL
D000818:Animals; D050260:Carbohydrate Metabolism; D003999:Dichloroacetic Acid; D004285:Dogs; D004789:Enzyme Activation; D005260:Female; D008066:Lipolysis; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009525:Niacin; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000502:physiology*
D011768:Pyruvate Dehydrogenase Complex; D009525:Niacin; D003999:Dichloroacetic Acid