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Estimating Gluconeogenic Rates in NIDDM

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New Concepts in the Pathogenesis of NIDDM

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 334))

Abstract

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.

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References

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  Google Scholar 

  4. J. Katz. Determination of gluconeogenesis in. vivo with 14C-labeled substrates. Am. J. Physiol.(Regulatory Integrative Comp. Physiol. 17) 248:R391–399 (1985).

    CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  8. B.R. Landau. Acetate’s metabolism, CO2 production and the TCA cycle. Am. J. Clin. Nutr. 53:981 (1991).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  17. R.R. Wolfe. Reply to B.R. Landau. Am. J. Clin. Nutr. 53:982 (1992).

    Google Scholar 

  18. B.R. Landau and J. Wahren. Nonproductive exchanges: The use of isotopes gone astray. Metabolism 41:457–459 (1992).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  21. A. Consoli, N. Nurjhan, D. Bier, and J.E. Gerich. Reply. Am. J. Physiol. 261 (Endocrinol. Metab. 24):E675–676 (1991).

    CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  30. R. Rognstad. Estimation of gluconeogenesis and glycogenolysis m vivo using tritiated water. Biochem. J. 279:911 (1991).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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. 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 

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Authors and Affiliations

  1. Department of Medicine School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA

    Bernard R. Landau

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  1. Bernard R. Landau
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Editors and Affiliations

  1. Karolinska Hospital, Stockholm, Sweden

    Claes Göran Östenson  & Suad Efendić  & 

  2. University of Toronto, Toronto, Ontario, Canada

    Mladen Vranic

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© 1993 Springer Science+Business Media New York

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Landau, B.R. (1993). Estimating Gluconeogenic Rates in NIDDM. In: Östenson, C.G., Efendić, S., Vranic, M. (eds) New Concepts in the Pathogenesis of NIDDM. Advances in Experimental Medicine and Biology, vol 334. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2910-1_15

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  • DOI: https://doi.org/10.1007/978-1-4615-2910-1_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6262-3

  • Online ISBN: 978-1-4615-2910-1

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