Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study

Journal of Clinical Investigation

Volumn 100, Issue 5, 1997, Pages 1305-1319

  Hellerstein, M K ^a,b,c   Neese, R A ^a,b   Linfoot, P ^a   Christiansen, M ^a   Turner, S ^b   Letscher, A ^a  

^a SAN FRANCISCO GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Carbohydrate metabolism; Glucuronate probe; Mass isotopomer distribution analysis (MIDA); Substrate cycles; UDP glucose

Indexed keywords

CARBON 13; GALACTOSE; GLUCAGON; GLYCEROL; GLYCOGEN; ISOTOPE; URIDINE DIPHOSPHATE GLUCOSE;

ARTICLE; CARBOHYDRATE METABOLISM; DIET RESTRICTION; GLUCONEOGENESIS; GLYCOGENOLYSIS; HUMAN; HUMAN EXPERIMENT; LIVER METABOLISM; NORMAL HUMAN; PRIORITY JOURNAL;

EID: 0030954707     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI119644     Document Type: Article

References (44)

1. Nilsson, L.H., P. Furst, and E. Hultman. 1973. Carbohydrate metabolism of the liver in normal man under varying dietary conditions. Scand. J. Clin. Lab. Invest. 32:331-337.
2. Consoli, A., F.P. Kennedy, J. Miles, and J.E. Gerich. 1987. Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J. Clin. Invest. 80:1303-1310.
3. 2O for estimating rates of gluconeogenesis. Application to the fasted state. J. Clin. Invest. 95:172-178.
4. Landau, B.R., J. Wahren, V. Chandramouli, W.C. Schumann, K. Ekberg, and S.C. Kalhan. 1995. Contributions to gluconeogenesis to glucose production in the fasted state. J. Clin. Invest. 98:378-385.
5. 13C-labeled lactate in man. Clin. Res. 42:28A.
6. Hellerstein, M., R. Neese, P. Linfoot, M. Christiansen, and A. Letscher. 1996. Detailed characterization in fasting humans of intrahepatic fluxes through gluconeogenesis (GNG) and glycogen. Diabetes. 45(Suppl. 2):36A.
7. 13C-NMR. Science (Wash. DC). 254:573-576.
8. Barrett, E.J., and Z. Liu. 1993. Hepatic glucose metabolism and insulin resistance in NIDDM and obesity. Bailliere's Clin. Endocrinol. Metab. 7(4): 875-901.
9. Stumvoll, M., U. Chintalapudi, G. Perriello, S. Welle, O. Gutierrez, and J. Gerich. 1995. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. J. Clin. Invest. 96:2528-2533.
10. Weinman, E.O., E.H. Strisower, and I.L. Chaikoff. 1957. Conversion of fatty acids to carbohydrate: applications of isotopes to this problem and the role of the Krebs cycle as a synthetic pathway. Physiol. Rev. 37: 252-272.
11. 14C]acetate and its use in assessing hepatic Krebs cycle activity and gluconeogenesis. J. Biol. Chem. 266: 6985-6990.
12. Hellerstein, M.K. 1995. Isotopic studies of carbohydrate metabolism in non-insulin-dependent diabetes mellitus. Curr. Opin. Endocrinol. Diab. 2:518-529.
13. Shikama, H., and M. Ui. 1978. Glucose load diverts hepatic gluconeogenic product from glucose to glycogen in vivo. Am. J. Physiol. 235:E354-E360.
14. Arion, W.J., A.J. Lange, H.E. Walls, and L.M. Ballas. 1980. Evidence for the participation of independent translocases for phosphate and glucose-6-phosphate in the microsomal glucose-6-phosphatase system. J. Biol. Chem. 255:10396-10406.
15. Rossetti, L., A. Giaccari, P. Barzilai, K. Howard, G. Sebel, and M. Hu. 1993. Mechanism by which hyperglycemia inhibits glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes. J. Clin. Invest. 92:1126-1134.
16. Hellerstein, M.K., R.A. Neese, J.-M. Schwarz, S. Turner, D. Faix, and K. Wu. 1997. Altered fluxes responsible for reduced hepatic glucose production and gluconeogenesis by exogenous glucose in rats. Am. J. Physiol. 272:E163-E172.
17. Barrett, E.J., S. Bevilacqua, R.A. DeFronzo, and E. Ferrannini. 1994. Glycogen turnover during refeeding in the post-absorptive dog: implications for the estimation of glycogen formation using tracer methods. Metab. Clin. Exp. 43:285-292.
18. Magnusson, I., D.L. Rothman, B. Jucker, G.W. Cline, R.G. Shulman, and G.I. Shulman. 1994. Liver glycogen turnover in fed and fasted humans. Am. J. Physiol. 266:E796-E803.
19. Jahoor, F., E.J. Peters, and R.R. Wolfe. 1990. The relationship between gluconeogenic substrate supply and glucose production in humans. Am. J. Physiol. 258:E288-E296.
20. Jenssen, T., N. Nurjhan, A. Consoli, and J.E. Gerich. 1990. Failure of substrate induced gluconeogenesis to increase overall glucose appearance without a change in plasma glucose concentration. J. Clin. Invest. 86:489-497.
21. Clore, J.N., and W.G. Blackard. 1994. Suppression of gluconeogenesis after a 3-day fast does not deplete liver glycogen in patients with NIDDM. Diabetes. 43:256-262.
22. Hellerstein, M.K., D.J. Greenblatt, and H.N. Munro. 1986. Glycoconjugates as non-invasive probes of intrahepatic metabolism. The pathway of glucose entry into compartmentalized hepatic UDP-glucose pools during feeding induced glycogen accumulation. Proc. Natl. Acad. Sci. USA. 83:7044-7048.
23. Hellerstein, M.K., S. Kaempfer, J.-M. Schwarz, K. Wu, and C.H.L. Shackleton. 1995. Rate of glucose entry into hepatic UDP-glucose by the direct pathway in fasted and fed states in normal humans. Metab. Clin. Exp. 44(2): 172-182.
24. Shulman, G.I., G. Cline, W.C. Shulman, V. Chandramouli, K. Kumaron, and R.R. Landau. 1990. Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans. Am. J. Physiol. 259:E335-E341.
25. Hellerstein, M.K., A. Letscher, J.-M. Schwarz, D. Cesar, C.H.L. Shackleton, S. Turner, R. Neese, K. Wu, S. Bock, and S. Kaempfer. 1997. Measurement of hepatic Ra UDP-glucose in vivo in rats: relation to glycogen deposition and labeling patterns. Am. J. Physiol. 272:E155-E162.
26. Neese, R.A., J.-M. Schwarz, D. Faix, S.M. Turner, A. Letscher, D. Vu, and M.K. Hellerstein. 1995. Gluconeogenesis and intrahepatic triosphosphate flux in response to fasting or substrate loads. Application of the mass isotopomer distribution analysis technique with testing of assumptions and potential problems. J. Biol. Chem. 270:14452-14463.
27. Neese, R.A., and M.K. Hellerstein. 1995. Appendix. Calculations for gluconeogenesis by mass isotopomer distribution analysis. J. Biol. Chem. 270: 14464-14466.
28. Dekker, E., M.K. Hellerstein, J.A. Romijn, R.A. Neese, N. Peshu, E. Endert, K. Marsh, and H. Sauerwein. 1997. Glucose homeostasis in children with falciparum malaria: precursor supply limits gluconeogenesis and glucose production. J. Clin. Endocrinol. Metab. In press.
29. Hellerstein, M.K. 1987. In vivo measurement of the appearance rate of hepatic UDP-glucose and partitioning of gluconeogenic flux in fasting and refed rats. Clin. Res. 35:505A.
30. Schwarz, J.-M., R.A. Neese, S. Turner, D. Dare, and M.K. Hellerstein. 1995. Short-term alterations in carbohydrate energy intake in humans: striking effects on hepatic glucose production, de novo lipogenesis, lipolysis and whole-body fuel selection. J. Clin. Invest. 96:2735-2743.
31. Steele, R. 1959. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann. NY Acad. Sci. 82:420-430.
32. Rother, K.I., and W.F. Schwenk. 1995. Hepatic glycogen accurately reflected by acetaminophen-glucuronide in dogs refed after fasting. Am. J. Physiol. 269:766-773.
33. Rother, K.I., and W.F. Schwenk. 1995. Glucose production in glycogen storage disease I is not associated with increased cycling through hepatic glycogen. Am. J. Physiol. 269:774-778.
34. Hellerstein, M.K., and R. Neese. 1992. Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. Am. J. Physiol. 263:E988-E1001.
35. Lehninger, A.L. 1975. Biochemistry. The molecular basis of cell structure and function. 2nd Ed. Worth Publishers, NY. Pp. 546, 620, 896, 934.
36. Ross, B., J. Tange, K. Emslie, S. Hart, M. Small, I. Calder. 1980. Paracetamol metabolism by the isolated perfused rat kidney. Kidney Int. 18:562-570.
37. Lowenthal, D.T., S. Oie, J.C. Van Stone, W.A. Briggs, G. Levy. 1976. Pharmacokinetics of acetaminophen elimination by anephric patients. J. Pharmacol. Exp. Ther. 196:570-578.
38. Magnusson, I., D.L. Rothman, D.P. Gerard, L.D. Katz, and G.I. Shulman. 1995. Contributions of hepatic glycogenolysis to glucose production in humans in response to a physiologic increase in plasma glucagon concentration. Diabetes. 44:185-189.
39. Henning, S.L., R.B. Wambolt, B.O. Schonekess, G.D. Lopaschuk, and M.F. Allard. 1996. Contribution of glycogen to aerobic myocardial glucose utilization. Circulation. 93(8):1549-1555.
40. Hers, H.G. 1976. The control of glycogen metabolism in the liver. Annu. Rev. Biochem. 45:167-189.
41. Previs, S.F., C.A. Fernandez, D. Yang, M.V. Soloviev, D. France, and H. Brunengraber. 1995. Limitations of the mass isotopomer distribution analysis of glucose to study gluconeogenesis substrate cycling between glycerol and triose phosphates in liver. J. Biol. Chem. 270:19806-19815.
42. 13C]glycerol and mass isotopomer distribution analysis of glucose. Am. J. Physiol. 269:E516-E523.
43. Ekberg, K., V. Chandramouli, K. Kumaran, W.C. Schuman, J. Wahren, and B.R. Landau. 1995. Gluconeogenesis and glucuronidation in liver in vivo and the heterogeneity of hepatocyte function. J. Biol. Chem. 270:21715-21717.
44. Nurjhan, N., A. Bucci, G. Perriello, M. Stumvoll, G. Dailey, D.M. Bier, I. Toft, T.G. Jenssen, and J.E. Gerich. 1995. Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man. J. Clin. Invest. 95: 272-277.