Estimation of pyruvate decarboxylation in perfused rat skeletal muscle

Schadewaldt, Peter; Münch, Ulrich; Prengel, Maria; Staib, W.

doi:10.1016/0006-291x(83)90545-4

Cited by 12 publications

(9 citation statements)

References 18 publications

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“…If the metabolism of the injected pyruvate was dominated by Krebs cycle metabolism, we would expect to detect a 13 CO 2 or H 13 CO 3 À signal. We did not find measurable signal at the relevant frequencies with our current detection limit, and most likely, the concentration of these metabolites is too low in resting muscles and tissue without energy demand (22,23). In the working heart muscle using a similar technique in pigs, we have detected and characterized the tissue metabolism by means of the H 13 CO 3 À metabolite.…”

Section: Discussionmentioning

confidence: 73%

Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

Golman¹,

Zandt²,

Lerche³

et al. 2006

Cancer Research

559

632

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The ''Warburg effect,'' an elevation in aerobic glycolysis, may be a fundamental property of cancer cells. For cancer diagnosis and treatment, it would be valuable if elevated glycolytic metabolism could be quantified in an image in animals and humans. The pyruvate molecule is at the metabolic crossroad for energy delivery inside the cell, and with a noninvasive measurement of the relative transformation of pyruvate into lactate and alanine within a biologically relevant time frame (seconds), it may be possible to quantify the glycolytic status of the cells. We have examined the metabolism after i.v. injection of hyperpolarized 13 C-pyruvate in rats with implanted P22 tumors. The strongly enhanced nuclear magnetic resonance signal generated by the hyperpolarization techniques allows mapping of pyruvate, lactate, and alanine in a 5 Â 5 Â 10 mm 3 imaging voxel using a 1.5 T magnetic resonance scanner. The magnetic resonance scanning (chemical shift imaging) was initiated 24 seconds after the pyruvate injection and had a duration of 14 seconds. All implanted tumors showed significantly higher lactate content than the normal tissue. The results indicate that noninvasive quantification of localized Warburg effect may be possible.

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Section: Discussionmentioning

confidence: 73%

Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

Golman¹,

Zandt²,

Lerche³

et al. 2006

Cancer Research

559

632

View full text Add to dashboard Cite

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“…and R.i.t.Z., unpublished results). It is more likely that the skeletal muscle tissue that constitutes most of the volume covered by the radiofrequency (rf)-coil does not metabolize pyruvate to a large extent through the tricarboxylic acid cycle in the resting muscular tissue of the anesthetized animal under the experimental conditions (15,16). Rates for pyruvate oxidation and formation of lactate and alanine have been calculated by using 13 C-glucose as substrate (17).…”

Section: Resultsmentioning

confidence: 99%

Real-time metabolic imaging

Golman¹,

Zandt²,

Thaning³

2006

Proc. Natl. Acad. Sci. U.S.A.

626

847

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The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...

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“…These ®ndings led us to investigate the possible sites whereby leptin stimulates glucose decarboxylation in skeletal muscle. We used both [1-14 C]-and [2-14 C]-pyruvate to trace the activities of pyruvate dehydrogenase (PDH) and Krebs cycle 17,24 in the presence of leptin and insulin. [1-14 C]-Pyruvate can either be decarboxylated to form acetyl CoA (via pyruvate dehydrogenase) or receive a carbon atom to generate oxaloacetate (via pyruvate carboxylase) to take part in the Krebs cycle.…”

Section: Discussionmentioning

confidence: 99%

Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation

1999

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OBJECTIVE: To investigate the effects of leptin and the combination of insulin and leptin on glucose metabolism in incubated rat soleus muscle. ANIMALS: Male lean albino rats (50 ± 70 g) of the Wistar strain were used in all experiments. MEASUREMENTS: 2-Deoxy-D-[ 3 H]-glucose (2-DG) uptake, glycogen synthesis, lactate synthesis, glucose and pyruvate decarboxylation. RESULTS: Leptin (1, 10 and 100 nM), increased 2-Deoxyglucose uptake from 4.07 AE AE 0.23 mmolah 71 ag 71 (basal) to 5.88 AE AE 0.29 m mmolah 71 ag 71 (100 nM) (P`0.05); however, leptin did not potentiate the effect of either physiological (100 mUaml) or supra-physiological (10 000 m mUaml) insulin concentrations on glucose uptake. Glycogen synthesis rose almost 2-fold in the presence of supra-physiological leptin concentrations (100 nM). The combination of insulin and leptin did not present any additional effect on glycogen synthesis beyond that caused by insulin. Compared to the control group, the decarboxylation of [U-14 C] D-glucose increased 75%, 246% and 304% (P`0.05) in the presence of 1, 10 and 100 nM leptin, respectively. When leptin (100 nM) was combined with insulin in the incubation medium, the 14 CO 2 production rose almost 4-fold (397%) (P`0.05) and more than 5-fold (527%) (P`0.05) for the 100 m mUaml and 10 000 mUaml insulin concentrations, respectively. In the presence of leptin (100 nM), the decarboxylation of [1-14 C]-and [2-14 C]-pyruvate in incubated muscles rose 89% and 49%, respectively, indicating that both pyruvate dehydrogenase and Krebs cycle are activated by leptin. CONCLUSION: These data demonstrate that, in soleus muscle, leptin per se exerts a direct and acute insulin-like effect, stimulating glucose uptake, glycogen synthesis, lactate formation and glucose oxidation.

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Estimation of pyruvate decarboxylation in perfused rat skeletal muscle

Cited by 12 publications

References 18 publications

Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

Real-time metabolic imaging

Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation

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