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1Center for NMR Research and Development, Division of Cardiovascular Disease, Department of Medicine, and 2Department of Physiology and Biophysics and The Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama 35294-4470
Submitted 20 December 2002 ; accepted in final form 4 March 2003
Despite the fact that lactate and pyruvate are potential substrates for
energy production in vivo, our understanding of the control and regulation of
carbohydrate metabolism is based principally on studies where glucose is the
only available carbohydrate. Therefore, the purpose of this study was to
determine the contributions of lactate, pyruvate, and glucose to energy
production in the isolated, perfused rat heart over a range of insulin
concentrations and after activation of pyruvate dehydrogenase with
dichloroacetate (DCA). Hearts were perfused with physiological concentrations
of [1-13C]glucose, [U-13C]lactate,
[2-13C]pyruvate, and unlabeled palmitate for 45 min. Hearts were
freeze clamped, and 13C NMR glutamate isotopomer analysis was
performed on tissue extracts. Glucose, lactate, and pyruvate all contributed
significantly to myocardial energy production; however, in the absence of
insulin, glucose contributed only 25–30% of total pyruvate oxidation.
Even under conditions where carbohydrates represented >95% of substrate
entering the tricarboxylic acid (TCA) cycle, we found that glucose contributed
at most 50–60% of total carbohydrate oxidation. Despite being present at
only 0.1 mM, pyruvate contributed between 
10% and 30% of total acetyl-CoA
entry into the TCA cycle. We also found that insulin and DCA not only
increased glucose oxidation but also exogenous pyruvate oxidation; however,
lactate oxidation was not increased. The differential effects of insulin and
DCA on pyruvate and lactate oxidation provide further evidence for
compartmentation of cardiac carbohydrate metabolism. These results may have
important implications for understanding the mechanisms underlying the
beneficial effects of increasing cardiac carbohydrate metabolism.
substrate metabolism; carbohydrates; fatty acids
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