Estimating Gluconeogenic Rates in NIDDM

  • Bernard R. Landau
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 334)


Lactate and alanine are the major precursors of glucose formed in liver by gluconeogenesis. However, incorporation of 14C, when those precursors are labeled with 14C, cannot be used to quantitate rates of gluconeogenesis. That is because an intermediate in the formation of the glucose is oxaloacetate, i.e. alanine and lactate → pyruvate → oxaloacetate → glucose, and oxaloacetate is also an intermediate in the tricarboxylic acid cycle(Figure 1). Consequently, labeled carbon in oxaloacetate, formed from the labeled precursors, exchanges with unlabeled carbon in oxaloacetate formed in the cycle from acetyl-CoA.


Krebs Cycle Tricarboxylic Acid Cycle Hepatic Glucose Production Liver Slice Liver Glycogen 
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  1. 1.
    E.H. Strisower, G.D. Kohler, and I.L. Chaikoff. Incorporation of acetate carbon into glucose by liver slices from normal and alloxan-diabetic rats. J. Biol. Chem. 198:115–120 (1952).PubMedGoogle Scholar
  2. 2.
    E.O. Weinman, E.H. Strisower, and I.L. Chaikoff. Conversion of fatty acids to carbohydrate. Application of isotopes to this problem and role of the Krebs cycle as a synthetic pathway. Physiol. Rev. 37:252–272 (1957).PubMedGoogle Scholar
  3. 3.
    G. Hetenyi, Jr. Correction for the metabolic exchange of 14C from 12C atoms in the pathway of gluconeogenesis in vivo. Fed. Proc. 41:104–109 (1982).PubMedGoogle Scholar
  4. 4.
    J. Katz. Determination of gluconeogenesis in. vivo with 14C-labeled substrates. Am. J. Physiol.(Regulatory Integrative Comp. Physiol. 17) 248:R391–399 (1985).Google Scholar
  5. 5.
    A. Consoli, F. Kennedy, J. Miles, and J. Gerich. Determination of Krebs cycle carbon exchange in_ vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J. Clin. Invest. 80:1303–1310 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Consoli, N. Nurjhan, F. Capani, and J. Gerich. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 38:550–557 (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    A. Consoli, and N. Nurjhan. Contribution of gluconeogenesis to overall glucose output in diabetic and non-diabetic men. Ann. Med. 22:191–195 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    B.R. Landau. Acetate’s metabolism, CO2 production and the TCA cycle. Am. J. Clin. Nutr. 53:981 (1991).PubMedGoogle Scholar
  9. 9.
    B. Bleiberg, T.R. Beers, M. Persson, and J.M. Miles. Systemic and regional acetate kinetics in dogs. Am. J. Physiol. 262 (Endocrinol. Metab. 25):E197–202 (1992).PubMedGoogle Scholar
  10. 10.
    J. Katz, and I.L. Chaikoff. Synthesis via the Krebs cycle in the utilization of acetate by rat liver slices. Biochim. Biophys. Acta. 18:87–101 (1955).PubMedCrossRefGoogle Scholar
  11. 11.
    W.C. Schumann, I. Magnusson, V. Chandramouli, K. Kumaran, J. Wahren, and B.R. Landau. Metabolism of [2-14C]acetate and its use in assessing hepatic Krebs cycle activity and gluconeogenesis. J. Biol. Chem. 266:6985–6990 (1991).PubMedGoogle Scholar
  12. 12.
    C. Des Rosiers, J.A. Montgomery, M. Garneau, F. David, O.A. Marner, P. Daloze, G. Toffolo, C. Cobelli, B.R. Landau, and H. Brunengraber. Pseudoketogenesis in hepatectomized dogs. Am. J. Physiol. 258 (Endocrinol. Metab. 21)E519–528 (1990).PubMedGoogle Scholar
  13. 13.
    I. Magnusson, W.C. Schumann, G.E. Bartsch, V. Chandramouli, K. Kumaran, J. Wahren, and B.R. Landau. Noninvasive tracing of Krebs cycle metabolism in liver. J. Biol. Chem. 266:6975–6984 (1991).PubMedGoogle Scholar
  14. 14.
    A. Consoli, N. Nurjhan, J.J. Reilly, Jr., D.M. Bier, and J.E. Gerich. Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans. Am. J. Physiol. 259 (Endocrinol. Metab. 22):E677–684 (1990).PubMedGoogle Scholar
  15. 15.
    A. Consoli, N. Nurjhan, J.J. Reilly, Jr., D.M. Bier, and J.E. Gerich. Mechanism of increased gluconeogenesis in noninsulin dependent diabetes mellitus: Role of alterations in systemic, hepatic and muscle lactate and alanine metabolism. J. Clin. Invest. 86:2038–2045 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    W. Kam, K. Kumaran, and B.R. Landau. Contribution of ω-oxidation to fatty acid oxidation by liver of rat and monkey. J. Lipid Res. 19:591–600 (1978).PubMedGoogle Scholar
  17. 17.
    R.R. Wolfe. Reply to B.R. Landau. Am. J. Clin. Nutr. 53:982 (1992).Google Scholar
  18. 18.
    B.R. Landau and J. Wahren. Nonproductive exchanges: The use of isotopes gone astray. Metabolism 41:457–459 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    G. Hetenyi Jr., B. Lussier, C. Ferrarotto, and J. Radziuk. Calculation of the rate of gluconeogenesis from the incorporation of 14C atoms from labeled bicarbonate or acetate. Can. J. Physiol. Pharmacol. 60:1603–1609 (1982).PubMedCrossRefGoogle Scholar
  20. 20.
    G. Hetenyi, Jr. Correction factor for estimation of plasma glucose synthesis from the transfer of 14C-atoms from labeled substrate m vivo: A preliminary report. Can. J. Physiol. Pharmacol. 57:767–770 (1979).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Consoli, N. Nurjhan, D. Bier, and J.E. Gerich. Reply. Am. J. Physiol. 261 (Endocrinol. Metab. 24):E675–676 (1991).Google Scholar
  22. 22.
    B.R. Landau. Correction of tricarboxylic acid cycle exchange in gluconeogenesis: Why the y’s are wrong? Am. J. Physiol. 261 (Endocrinol. Metab. 24):E673–674 (1991).PubMedGoogle Scholar
  23. 23.
    J. Wahren, S. Efendic, R. Luft, L. Hagenfeldt, O. Bjorkman, and P. Felig. Influence of somatomedin on splanchnic glucose metabolism in postabsorptive and 60-hour fasted humans. J. Clin. Invest. 59:299–307 (1977).PubMedCrossRefGoogle Scholar
  24. 24.
    R. Kibler, W. Taylor, and J. Myers. The effect of glucagon on net splanchnic balances of glucose, amino acid, nitrogen, urea, ketones and oxygen in man. J. Clin. Invest. 43:904–915 (1964).PubMedCrossRefGoogle Scholar
  25. 25.
    D.E. Matthews and R.S. Downey. Measurements of urea kinetics in humans: a validation of stable isotope tracer methods. Am. J. Physiol. 246 (Endocrinol. Metab. 9):E519–E529 (1984).PubMedGoogle Scholar
  26. 26.
    E. Esenmo, V. Chandramouli, W.C. Schumann, K. Kumaran, J. Wahren, and B.R. Landau. Use of 14CO2 in estimating rates of hepatic gluconeogenesis. Am. J. Physiol. 263 (Endocrinol. Metab. 26):E36–41 (1992).PubMedGoogle Scholar
  27. 27.
    D.L. Rothman, I. Magnusson, L.D. Katz, R.G. Shulman and G.I. Shulman. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C-NMR. Science 54:573–576 (1991).CrossRefGoogle Scholar
  28. 28.
    B. Kunnecke and J. Seelig. Glycogen metabolism as detected by m vivo and m vitro 13C-NMR spectroscopy using [1,2-13C2]glucose as substrate. Biochim. Biophys. Acta. 1095:103–113 (1991).PubMedCrossRefGoogle Scholar
  29. 29.
    L.O. Sillerud and R.G. Shulman. Structure and metabolism of mammalian liver glycogen monitored by carbon 13 nuclear magnetic resonance. Biochemistry 22:1087–1094 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    R. Rognstad. Estimation of gluconeogenesis and glycogenolysis m vivo using tritiated water. Biochem. J. 279:911 (1991).PubMedGoogle Scholar
  31. 31.
    M. Kuwajima, S. Golden, J. Katz, R.H. Unger, D.W. Foster and J.D. McGarry. Active hepatic glycogen synthesis from gluconeogenic precursors despite high tissue levels of fructose 2,6-bisphosphate. J. Biol. Chem. 261:2632–2637 (1986).PubMedGoogle Scholar
  32. 32.
    L. Ljungdahl, H.G. Wood, E. Racker, and D. Court. Formation of unequally labeled fructose-6-phosphate by an exchange reaction catalyzed by transaldolase. J. Biol. Chem. 236:1622–1625 (1961).PubMedGoogle Scholar
  33. 33.
    D. Faix, R. Neese, and M.K. Hellerstein. Measurement of gluconeogenesis in vivo using mass isotopomer distribution analysis. FASEB(Abstract) 6:A1788 (1992).Google Scholar
  34. 34.
    J.K. Kelleher, and A.L. Holleran. Model equations estimating gluconeogensis and glycogenolysis as components of hepatic glucose output using 13C tracers. FASEB(Abstract) 6:A3167 (1992).Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Bernard R. Landau
    • 1
  1. 1.Department of Medicine School of MedicineCase Western Reserve UniversityClevelandUSA

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