Contributions of gluconeogenesis to glucose production in the fasted state
Open accessAbstract
Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the postabsorptive state, ~70-75% of glucose uptake occurs in insulin-insensitive tissues, with only ~25% in insulin-sensitive tissues.
“In the postabsorptive state, the majority (∼70–75%) of glucose uptake (∼2 mg/kg per min) occurs in insulin-insensitive tissues (brain, erythrocytes, and splanchnic tissues) ( 17 , 18 ), with only ∼25% of glucose uptake occurring in insulin-sensitive tissues.”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [17]
The Discussion (page unavailable) reports percentages for gluconeogenesis as a contribution to glucose production, not for glucose uptake by insulin-sensitive or insulin-insensitive tissues. Searches for the 70–75%/25% tissue split and the named tissues found no passage addressing that claim in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSimilar approaches focusing on a handful of metabolites have already been used successfully in humans to measure gluconeogenesis and the urea cycle in vivo, and to compare metabolism between lung tumors and surrounding tissue.
“Similar approaches focusing on a handful of metabolites have already been used successfully in humans to measure gluconeogenesis and the urea cycle in vivo, and to compare metabolism between lung tumors and surrounding tissue (Fan et al., 2009; Landau et al., 1996; Yudkoff et al., 2010).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Landau et al., 1996
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · see citing works
Magnusson, I., Rothman, D. L., Katz, L. D., Shulman, R. G., & Shulman, G. I. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115997 · Cited by 757 · see citing works
THE EFFECT OF ARSENATE ON AEROBIC PHOSPHORYLATION
Crane, R. K., & Lipmann, F. A. (1953) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71364-1 · Cited by 546 · see citing works
Rothman, D. L., Magnusson, I., Katz, L. D., Shulman, R. G., & Shulman, G. I. (1991) · Science · doi:10.1126/science.1948033 · Cited by 546 · see citing works
Williamson, D. H., & Mellanby, J. H. (1974) · Elsevier eBooks · doi:10.1016/b978-0-12-091304-6.50037-9 · Cited by 444 · see citing works
Stümvoll, M., Chintalapudi, U., Perriello, G., Welle, S. L., Gutiérrez, O. M., & Gerich, J. E. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118314 · Cited by 280 · see citing works
Nilsson, L. H., & Hultman, E. (1973) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517309084355 · Cited by 263 · see citing works
Intramolecular Hydrogen Transfer in the Phosphoglucose Isomerase Reaction
Rose, I. A., & O'Connell, E. L. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93975-x · Cited by 197 · see citing works
Nurjhan, N., Consoli, A., & Gerich, J. E. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115558 · Cited by 194 · see citing works
Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state.
Landau, B. R., Wahren, J., Chandramouli, V., Schumann, W. C., Ekberg, K., & Kalhan, S. C. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117635 · Cited by 173 · see citing works
Self-citationConsoli, A., Kennedy, F., Miles, J., & Gerich, J. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113206 · Cited by 170 · see citing works
Ljungdahl, L. G., Wood, H. G., Racker, E., & Couri, D. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63274-6 · Cited by 167 · see citing works
Hormonal control of substrate cycling in humans.
Miyoshi, H., Shulman, G. I., Peters, E. J., Wolfe, M. H., Elahi, D., & Wolfe, R. R. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113487 · Cited by 139 · see citing works
The Estimation of Primary Carbinol Groups in Carbohydrates
Reeves, R. E. (1941) · Journal of the American Chemical Society · doi:10.1021/ja01850a509 · Cited by 136 · see citing works
Wahren, J., Efendić, S., Luft, R., Hagenfeldt, L., Björkman, O., & Felig, P. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108641 · Cited by 128 · see citing works
Self-citationButler, P. C., & Rizza, R. A. (1991) · Diabetes · doi:10.2337/diab.40.1.73 · Cited by 127 · see citing works
Petersen, K. F., Price, T. B., Cline, G. W., Rothman, D. L., & Shulman, G. I. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.1.e186 · Cited by 126 · see citing works
Neese, R. A., Schwarz, J., Faix, D. J., Turner, S., Letscher, A., Vu, D., & Hellerstein, M. K. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.24.14452 · Cited by 125 · see citing works
A new color reaction for the determination of aldopentose in presence of other saccharides
Dische, Z., & Borenfreund, E. (1957) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(57)90387-6 · Cited by 123 · see citing works
Gluconeogenesis: methodological approaches in vivo.
Chiasson, J. L., LILJENQUIST, J. E., LACY, W. W., As, J., & Cherrington, A. D. (1977) · PubMed · Cited by 120 · see citing works
Liver glycogen turnover in fed and fasted humans
Magnusson, I., Rothman, D. L., Jucker, B. M., Cline, G. W., Shulman, R. G., & Shulman, G. I. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.5.e796 · Cited by 107 · see citing works
Shulman, G. I., Ladenson, P. W., WOLFE, M. H., Ridgway, E. C., & Wolfe, R. R. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112032 · Cited by 102 · see citing works
Kuwajima, M., Golden, S., Katz, J. J., Unger, R. H., Foster, D. W., & McGarry, J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35834-9 · Cited by 97 · see citing works
Schumann, W. C., Magnusson, I., Chandramouli, V., Kumaran, K., Wahren, J., & Landau, B. R. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)89599-4 · Cited by 85 · see citing works
Self-citationGlycogen Turnover in the Isolated Working Rat Heart
Goodwin, G. W., Arteaga, J. R., & Taegtmeyer, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9234 · Cited by 83 · see citing works
The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.
Rooney, D. P., Neely, R. D., Cullen, C., Ennis, C. N., Sheridan, B., Atkinson, A. B., Trimble, E. R., & Bell, P. M. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.5.8077310 · Cited by 76 · see citing works
Glucose Synthesis in Tritiated Water
Rognstad, R., Katz, J. J., & Clark, D. G. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03703.x · Cited by 70 · see citing works
Validation of 13C NMR measurements of liver glycogen in vivo
Rolf Gruetter, A., Magnusson, I., Rothman, D. L., Avison, M. J., Shulman, R. G., & Shulman, G. I. (1994) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910310602 · Cited by 69 · see citing works
Björkman, O., Felig, P., & Wahren, J. (1980) · Diabetes · doi:10.2337/diab.29.8.610 · Cited by 59 · see citing works
Self-citationBjörkman, O., Eriksson, L. S., Nyberg, B., & Wahren, J. (1990) · Diabetes · doi:10.2337/diab.39.6.747 · Cited by 54 · see citing works
Self-citationA non- invasive assessment of hepatic glycogen kinetics and post- absorptive gluconeogenesis in man
Gay, L. J., Schneiter, P., Schutz, Y., Vetta, V. D., Jéquier, E., & Tappy, L. (1994) · Diabetologia · doi:10.1007/s001250050141 · Cited by 53 · see citing works
Influence of hyperthyroidism on splanchnic exchange of glucose and gluconeogenic precursors.
Wahren, J., Wennlund, A., Nilsson, L. H., & Felig, P. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110117 · Cited by 52 · see citing works
Self-citationMeasuring gluconeogenesis with [2-13C]glycerol and mass isotopomer distribution analysis of glucose
Peroni, O. D., Large, V., & Beylot, M. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.3.e516 · Cited by 50 · see citing works
Insulin dissociates hepatic glucose cycling and glucagon-induced thermogenesis in man
Calles-Escandón, J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90180-5 · Cited by 49 · see citing works
879. Cytidine diphosphate ribitol from Lactobacillus arabinosus
BADDILEY, J., BUCHANAN, J. G., Carss, B., & Mathias, A. P. (1956) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9560004583 · Cited by 48 · see citing works
Björkman, O., Gunnarsson, R., Hagström, E., Felig, P., & Wahren, J. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113884 · Cited by 48 · see citing works
Self-citationGuo, Z., Lee, W.-N. P., Katz, J. J., & Bergner, A. E. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90238-3 · Cited by 42 · see citing works
Landau, B. R., Fernandez, C. A., Previs, S. F., Ekberg, K., Chandramouli, V., Wahren, J., Kalhan, S. C., & Brunengraber, H. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.1.e18 · Cited by 42 · see citing works
Self-citationTesting of the assumptions made in estimating the extent of futile cycling
Wajngot, A., Chandramouli, V., Schumann, W. C., Kumaran, K., Efendić, S., & Landau, B. R. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.5.e668 · Cited by 39 · see citing works
Self-citationGlucose and fructose 6-phosphate cycle in humans
Karlander, S. G., Roovete, A., Vranić, M., & Efendić, S. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.5.e530 · Cited by 33 · see citing works
Estimating Gluconeogenic Rates in NIDDM
Landau, B. R. (1993) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-2910-1_15 · Cited by 30 · see citing works
Self-citationInfluence of Arginine on Splanchnic Glucose Metabolism in Man
Bratusch-Marrain, P. R., Björkman, O., Hagenfeldt, L., Waldhäusl, W., & Wahren, J. (1979) · Diabetes · doi:10.2337/diab.28.2.126 · Cited by 29 · see citing works
Self-citationJackson, E. L. (2011) · Organic reactions · doi:10.1002/0471264180.or002.08 · Cited by 28 · see citing works
Estimation of glucose turnover with stable tracer glucose-1-13C.
Kalhan, S. C., Savin, S. M., & Adam, P. A. J. (1977) · PubMed · Cited by 28 · see citing works
Self-citationKalhan, S. C., Trivedi, R., Singh, S. K., Chandramouli, V., Schumann, W. C., & Landau, B. R. (1995) · Journal of Mass Spectrometry · doi:10.1002/jms.1190301111 · Cited by 24 · see citing works
Self-citationGlucose Turnover in Hyperthyroid Patients with Normal Glucose Tolerance*
Karlander, S., Khan, A., Wajngot, A., Törring, O., Vranić, M., & Efendić, S. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-4-780 · Cited by 24 · see citing works
Preparation of 1-C14-D-Xylose from 1-C14-D-Glucose
Sowden, J. C. (1951) · Journal of the American Chemical Society · doi:10.1021/ja01155a563 · Cited by 22 · see citing works
Quantitation of glycogen/glucose-1-P cycling in liver
Wajngot, A., Chandramouli, V., Schumann, W. C., Efendic, S., & Landau, B. R. (1991) · Metabolism · doi:10.1016/0026-0495(91)90019-s · Cited by 18 · see citing works
Self-citationGlycogen: its mode of formation and contribution to hepatic glucose output in postabsorptive humans
Pimenta, W. P., Nurjhan, N., Jansson, P., Stümvoll, M., Gerich, J. E., & Korytkowski, M. T. (1994) · Diabetologia · doi:10.1007/bf00417694 · Cited by 18 · see citing works
Bjorkman, O., Ls, E., Nyberg, B., et al. (1990) · Diabetes · doi:10.2337/diabetes.39.6.747 · Cited by 17 · see citing works
Fructose-6-Phosphate Cycling and the Pentose Cycle in Hyperthyroidism
Magnusson, I., Wennlund, A., Chandramouli, V., Schumann, W. C., Kumaran, K., Wahren, J., & Landau, B. R. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-2-461 · Cited by 14 · see citing works
Self-citationA quantitative study of glucagon-induced hepatic glycogenolysis
Landau, B. R., Leonards, J. R., & Barry, F. M. (1960) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1960.199.2.231 · Cited by 12 · see citing works
Self-citationStetten, M. R., & Kehoe, J. J. (1971) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(71)90250-6 · Cited by 5 · see citing works
Influence of arginine on splanchnic glucose metabolism in man
Bratusch-Marrain, P. R., Björkman, O., Hagenfeldt, L., et al. (1979) · Diabetes · doi:10.2337/diabetes.28.2.126 · Cited by 5 · see citing works
Glycogen: its mode of formation and contribution to hepatic glucose output in postabsorptive humans
Pimenta, W., Nurjhan, N., Jansson, P. A., et al. (1994) · Diabetologia · doi:10.1007/s001250050166 · Cited by 5 · see citing works
Enzymatic determination of 1-14C-glucose in pig plasma
Sch�ffer, L., & Tronier, B. (1989) · Diabetologia · doi:10.1007/bf00274253 · Cited by 3 · see citing works
Björkman, O., Felig, P., & Wahren, J. (1984) · Clinical Physiology · doi:10.1111/j.1475-097x.1984.tb00117.x · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-s302 · Cited by 2,102 · see citing works
Regulation of hepatic glucose metabolism in health and disease
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.80 · Cited by 1,131 · see citing works
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V, Chandramouli, V, Inzucchi, S. E., Schumann, W. C., Petersen, K. F., Landau, B. R., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2063 · Cited by 1,052 · see citing works
Self-citationGao, X., Wu, G., Gu, X., Fu, L., & Mei, C. (2013) · Kidney & Blood Pressure Research · doi:10.1159/000355743 · Cited by 1,036 · see citing works
Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
DeBerardinis, R. J., & Thompson, C. B. (2012) · Cell · doi:10.1016/j.cell.2012.02.032 · Cited by 858 · see citing works
Gerich, J. E. (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02894.x · Cited by 634 · see citing works
Gastaldelli, A., Cusi, K., Pettiti, M., Hardies, J., Miyazaki, Y., Berria, R., Buzzigoli, E., Sironi, A. M., Cersosimo, E., Ferrannini, E., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.04.068 · Cited by 629 · see citing works
Marin-Valencia, I., Yang, C., Mashimo, T., Cho, S., Baek, H., Yang, X.-L., Rajagopalan, K. N., Maddie, M., Vemireddy, V., Zhao, Z., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.05.001 · Cited by 529 · see citing works
Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498 · see citing works
Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo.
Cherrington, A. D. (1999) · Diabetes · doi:10.2337/diabetes.48.5.1198 · Cited by 500 · see citing works
Diacylglycerol-mediated insulin resistance
Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 493 · see citing works
NADPH Oxidases, Reactive Oxygen Species, and the Kidney
Sedeek, M. H., Nasrallah, R., Touyz, R. M., & Hébert, R. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012111112 · Cited by 460 · see citing works
Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2006) · Metabolic Engineering · doi:10.1016/j.ymben.2006.01.004 · Cited by 451 · see citing works
Degn, K. B., Juhl, C. B., Sturis, J., Jakobsen, G., Brock, B., Chandramouli, V., Rungby, J., Landau, B. R., & Schmitz, O. (2004) · Diabetes · doi:10.2337/diabetes.53.5.1187 · Cited by 427 · see citing works
Self-citationMiyazaki, Y., Mahankali, A., Matsuda, M., Glass, L., Mahankali, S., Ferrannini, E., Cusi, K., Mandarino, L. J., & DeFronzo, R. A. (2001) · Diabetes Care · doi:10.2337/diacare.24.4.710 · Cited by 407 · see citing works
Satapati, S., Sunny, N. E., Kucejova, B., Fu, X., He, T. T., Méndez-Lucas, A., Shelton, J. M., Perales, J. C., Browning, J. D., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m023382 · Cited by 407 · see citing works
Targeting hepatic glucose metabolism in the treatment of type 2 diabetes
Rines, A. K., Sharabi, K., Tavares, C. D. J., & Puigserver, P. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.151 · Cited by 380 · see citing works
Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo
Feyter, H. M. D., Behar, K. L., Corbin, Z. A., Fulbright, R. K., Brown, P. B., McIntyre, S., Nixon, T. W., Rothman, D. L., & de Graaf, R. A. (2018) · Science Advances · doi:10.1126/sciadv.aat7314 · Cited by 378 · see citing works
Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.
Rizza, R. A. (2010) · Diabetes · doi:10.2337/db10-1032 · Cited by 367 · see citing works
Gastaldelli, A., Baldi, S., Pettiti, M., Toschi, E., Camastra, S., Natali, A., Landau, B. R., & Ferrannini, E. (2000) · Diabetes · doi:10.2337/diabetes.49.8.1367 · Cited by 320 · see citing works
Self-citationMetformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase
Hunter, R. W., Hughey, C. C., Lantier, L., Sundelin, E. I., Peggie, M., Zeqiraj, E., Sicheri, F., Jessen, N., Wasserman, D. H., & Sakamoto, K. (2018) · Nature Medicine · doi:10.1038/s41591-018-0159-7 · Cited by 313 · see citing works
Roden, M., Stingl, H., Chandramouli, V, Schumann, W. C., Hofer, A., Landau, B. R., Nowotny, P., Waldhäusl, W., & Shulman, G. I. (2000) · Diabetes · doi:10.2337/diabetes.49.5.701 · Cited by 288 · see citing works
The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects
Chen, X., Iqbal, N., & Boden, G. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5479 · Cited by 291 · see citing works
Metabolic Effects of Visceral Fat Accumulation in Type 2 Diabetes
Gastaldelli, A., Miyazaki, Y., Pettiti, M., Matsuda, M., Mahankali, S., Santini, E., DeFronzo, R. A., & Ferrannini, E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020696 · Cited by 289 · see citing works
A guide to 13C metabolic flux analysis for the cancer biologist
Antoniewicz, M. R. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0060-y · Cited by 264 · see citing works
Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus
Treadway, J. L., Mendys, P., & Hoover, D. J. (2001) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.10.3.439 · Cited by 260 · see citing works
Renal glucose production and utilization: new aspects in humans
Stümvoll, M., Meyer, C., Mitrakou, A., Nadkarni, V., & Gerich, J. E. (1997) · Diabetologia · doi:10.1007/s001250050745 · Cited by 258 · see citing works
Phosphoenolpyruvate Carboxykinase Is Necessary for the Integration of Hepatic Energy Metabolism
She, P., Shiota, M., Shelton, K. D., Chalkley, R. G., Postic, C., & Magnuson, M. A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.17.6508-6517.2000 · Cited by 257 · see citing works
Cappel, D. A., Deja, S., Duarte, J. A. G., Kucejova, B., Iñigo, M., Fletcher, J. A., Fu, X., Berglund, E. D., Liu, T., Elmquist, J. K., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.014 · Cited by 242 · see citing works
FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis
Boden, G. H., Cheung, P., Stein, T. P., Kresge, K. M., & Mozzoli, M. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00429.2001 · Cited by 248 · see citing works
Regulation of Gluconeogenesis by Krüppel-like Factor 15
Gray, S., Wang, B., Orihuela, Y., Hong, E., Fisch, S., Haldar, S. M., Cline, G. W., Kim, J. K., Peroni, O. D., Kahn, B. B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.03.002 · Cited by 246 · see citing works
Kuriyama, H., Shimomura, I., Kishida, K., Kondo, H., Furuyama, N., Nishizawa, H., Maeda, N., Matsuda, M., Nagaretani, H., Kihara, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2915 · Cited by 243 · see citing works
Dimitriadis, G. D., Maratou, E., Kountouri, A., Board, M., & Lambadiari, V. (2021) · Nutrients · doi:10.3390/nu13010159 · Cited by 241 · see citing works
Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo
Martin, W. H., Hoover, D. J., Armento, S. J., Stock, I. A., McPherson, R. K., Danley, D. E., Stevenson, R. W., Barrett, E. J., & Treadway, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1776 · Cited by 232 · see citing works
Role of glutamine in human carbohydrate metabolism in kidney and other tissues
Stümvoll, M., Perriello, G., Meyer, C., & Gerich, J. E. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.055003778.x · Cited by 230 · see citing works
A Review of Issues of Dietary Protein Intake in Humans
Bilsborough, S., & Mann, N. J. (2006) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.16.2.129 · Cited by 227 · see citing works
Glucose Control by the Kidney: An Emerging Target in Diabetes
Marsenić, O. (2009) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2008.12.031 · Cited by 217 · see citing works
Basu, R., Chandramouli, V., Dicke, B. A., Landau, B. R., & Rizza, R. A. (2005) · Diabetes · doi:10.2337/diabetes.54.7.1942 · Cited by 190 · see citing works
Self-citationHaddad, P. S., Eid, H., Nachar, A., Thong, F. S. L., & Sweeney, G. (2015) · Pharmacognosy Magazine · doi:10.4103/0973-1296.149708 · Cited by 189 · see citing works
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study.
Hellerstein, M. K., Neese, R. A., Linfoot, P., Christiansen, M., Turner, S., & Letscher, A. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119644 · Cited by 188 · see citing works
Physiology of glucose homeostasis
Gerich, J. E. (2000) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2000.00085.x · Cited by 186 · see citing works
Splanchnic regulation of glucose production
Wahren, J., & Ekberg, K. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093806 · Cited by 185 · see citing works
Self-citationBurgess, S. C., Hausler, N., Merritt, M. E., Jeffrey, F. M. H., Storey, C. J., Milde, A., Koshy, S., Lindner, J., Magnuson, M. A., Malloy, C. R., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407120200 · Cited by 178 · see citing works
Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation
Soeters, M. R., Soeters, P. B., Schooneman, M. G., Houten, S. M., & Romijn, J. A. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00397.2012 · Cited by 177 · see citing works
The evolutionary benefit of insulin resistance
Soeters, M. R., & Soeters, P. B. (2012) · Clinical Nutrition · doi:10.1016/j.clnu.2012.05.011 · Cited by 176 · see citing works
Boden, G. H., Chen, X., Capulong, E., & Mozzoli, M. A. (2001) · Diabetes · doi:10.2337/diabetes.50.4.810 · Cited by 175 · see citing works
SGLT2 inhibitors in the treatment of type 2 diabetes
Hasan, F., Alsahli, M., & Gerich, J. E. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.02.014 · Cited by 175 · see citing works
Renal glucose metabolism in normal physiological conditions and in diabetes
Alsahli, M., & Gerich, J. E. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2017.07.033 · Cited by 173 · see citing works
Hirsch, K. R., Wolfe, R. R., & Ferrando, A. A. (2021) · Nutrients · doi:10.3390/nu13051675 · Cited by 173 · see citing works
Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity
Stümvoll, M., Meyer, C., Perriello, G., Kreider, M. E., Welle, S. L., & Gerich, J. E. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.5.e817 · Cited by 173 · see citing works
Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet
Veldhorst, M. A., Westerterp-Plantenga, M. S., & Westerterp, K. R. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27834 · Cited by 170 · see citing works
Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus
Boden, G. H., Chen, X., & Stein, T. P. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e23 · Cited by 167 · see citing works
Sabir, S., Akash, M. S. H., Fiayyaz, F., Saleem, U., Mehmood, M. H., & Rehman, K. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108802 · Cited by 165 · see citing works
Renal substrate exchange and gluconeogenesis in normal postabsorptive humans
Meyer, C., Stümvoll, M., Dostou, J. M., Welle, S. L., Haymond, M. W., & Gerich, J. E. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00116.2001 · Cited by 162 · see citing works
Browning, J. D., Baxter, J., Satapati, S., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p020867 · Cited by 160 · see citing works
Xu, J., Xiao, G. G., Trujillo, C., Chang, V. C., Blanco, L., Joseph, S. B., Bassilian, S., Saad, M. F., Tontonoz, P., Lee, W. N. P., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201208200 · Cited by 158 · see citing works
Quantifying gluconeogenesis during fasting
Chandramouli, V., Ekberg, K., Schumann, W. C., Kalhan, S. C., Wahren, J., & Landau, B. R. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.6.e1209 · Cited by 154 · see citing works
Self-citationGastaldelli, A., Toschi, E., Pettiti, M., Frascerra, S., Quiñones-Galvan, A., Sironi, A. M., Natali, A., & Ferrannini, E. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1807 · Cited by 150 · see citing works
Nuttall, F. Q., Ngo, A., & Gannon, M. C. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.863 · Cited by 146 · see citing works
Renal Gluconeogenesis: An Underestimated Role of the Kidney in Systemic Glucose Metabolism
Legouis, D., Faivre, A., Cippà, P. E., & de Seigneux, S. (2022) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaa302 · Cited by 151 · see citing works
Bock, G., Chittilapilly, E. G., Basu, R., TOFFOLO, G. M., Cobelli, C., Chandramouli, V., Landau, B. R., & Rizza, R. A. (2007) · Diabetes · doi:10.2337/db06-1776 · Cited by 146 · see citing works
Self-citationFaria, M. H. C. P., de Aguilar‐Nascimento, J. E., Pimenta, O. S., Alvarenga, L. C., Dock‐Nascimento, D. B., & Slhessarenko, N. (2009) · World Journal of Surgery · doi:10.1007/s00268-009-0010-x · Cited by 143 · see citing works
Doi, M., Yamaoka, I., Nakayama, M., Sugahara, K., & Yoshizawa, F. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00609.2006 · Cited by 141 · see citing works
Gluconeogenesis and hepatic glycogenolysis during exercise at the lactate threshold
Emhoff, C.-A. W., Messonnier, L. A., Horning, M. A., Fattor, J. A., Carlson, T. J., & Brooks, G. A. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01202.2012 · Cited by 139 · see citing works
Measuring Deuterium Enrichment of Glucose Hydrogen Atoms by Gas Chromatography/Mass Spectrometry
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2011) · Analytical Chemistry · doi:10.1021/ac200012p · Cited by 137 · see citing works
Direct and indirect effects of amino acids on hepatic glucose metabolism in humans
Krebs, M., Brehm, A., Krššák, M., Anderwald, C. H., Bernroider, E., Nowotny, P., Roth, E., Chandramouli, V., Landau, B. R., Waldh�usl, W., et al. (2003) · Diabetologia · doi:10.1007/s00125-003-1129-1 · Cited by 134 · see citing works
Self-citationOrho, M., Bosshard, N. U., Buist, N. R. M., GITZELMANN, R., Aynsley-Green, A., Blümel, P., Gannon, M. C., Nuttall, F. Q., & Groop, L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2890 · Cited by 126 · see citing works
Wajngot, A., Chandramouli, V., Schumann, W. C., Ekberg, K., Jones, P. K., Efendic, S., & Landau, B. R. (2001) · Metabolism · doi:10.1053/meta.2001.19422 · Cited by 128 · see citing works
Self-citationEdgerton, D. S., Cardin, S., Emshwiller, M., Neal, D. W., Chandramouli, V., Schumann, W. C., Landau, B. R., Rossetti, L., & Cherrington, A. D. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1872 · Cited by 127 · see citing works
Self-citationGómez-Valadés, A. G., Méndez‐Lucas, A., Vidal‐Alabró, A., Blasco, F. X., Chillón, M., Bartrons, R., Bermúdez, J., & Perales, J. C. (2008) · Diabetes · doi:10.2337/db07-1087 · Cited by 123 · see citing works
Brown, S., Zhang, Y.-H., & Walker, S. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.11.011 · Cited by 122 · see citing works
An integrated2H and13C NMR study of gluconeogenesis and TCA cycle flux in humans
Jones, J. G., Solomon, M. A., Cole, S., Sherry, A. D., & Malloy, C. R. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.4.e848 · Cited by 121 · see citing works
Patterson, B. W., Mittendorfer, B., Elias, N., Satyanarayana, R., & Klein, S. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30164-4 · Cited by 118 · see citing works
Gastaldelli, A., Miyazaki, Y., Pettiti, M., Buzzigoli, E., Mahankali, S., Ferrannini, E., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031941 · Cited by 117 · see citing works
Webster, C. C., Noakes, T. D., Chacko, S. K., Swart, J., Kohn, T. A., & Smith, J. A. H. (2016) · The Journal of Physiology · doi:10.1113/jp271934 · Cited by 115 · see citing works
Effects of Free Fatty Acids Per Se on Glucose Production, Gluconeogenesis, and Glycogenolysis
Stæhr, P., Nielsen, O. H., Landau, B. R., Chandramouli, V., Holst, J. J., & Beck‐Nielsen, H. (2003) · Diabetes · doi:10.2337/diabetes.52.2.260 · Cited by 114 · see citing works
Self-citationThe application of 2H2O to measure skeletal muscle protein synthesis
Gasier, H. G., Fluckey, J. D., & Previs, S. F. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-31 · Cited by 113 · see citing works
Mechanisms by Which Liver-Specific PEPCK Knockout Mice Preserve Euglycemia During Starvation
She, P., Burgess, S. C., Shiota, M., Flakoll, P. J., Donahue, E. P., Malloy, C. R., Sherry, A. D., & Magnuson, M. A. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1649 · Cited by 112 · see citing works
Stark, R., & Kibbey, R. (2013) · Biochimica et Biophysica Acta · doi:10.1016/j.bbagen.2013.10.033 · Cited by 101 · see citing works
Kaur, R., Dahiya, L., & Kumar, M. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.09.029 · Cited by 111 · see citing works
Glucose turnover and gluconeogenesis in human pregnancy.
Kalhan, S. C., Rossi, K., Gruca, L. L., Burkett, E., & O’Brien, A. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119704 · Cited by 107 · see citing works
Self-citationGlucose homeostasis, obesity and diabetes
Bano, G. (2013) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2013.02.007 · Cited by 104 · see citing works
Calamita, G., Gena, P., Ferri, D., Rosito, A., Rojek, A., Nielsen, S., Marinelli, R. A., Frühbeck, G., & Svelto, M. (2012) · Biology of the Cell · doi:10.1111/boc.201100061 · Cited by 102 · see citing works
APPLICATIONS OF MASS ISOTOPOMER ANALYSISTO NUTRITION RESEARCH
Brunengraber, H., Kelleher, J. K., & Rosiers, C. D. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.559 · Cited by 102 · see citing works
Gluconeogenesis and the Cori cycle in 12-, 20-, and 40-h-fasted humans
Katz, J. J., & Tayek, J. A. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.3.e537 · Cited by 102 · see citing works
Mechanism of ER Stress and Inflammation for Hepatic Insulin Resistance in Obesity
Kim, O., Jun, W., & Lee, J. (2015) · Annals of Nutrition and Metabolism · doi:10.1159/000440905 · Cited by 100 · see citing works
Indole-2-carboxamide Inhibitors of Human Liver Glycogen Phosphorylase
Hoover, D. J., Snow, S. L., Burgess‐Henry, J., Martin, W. H., Armento, S. J., Stock, I. A., McPherson, R. K., Genereux, P. E., Gibbs, E. M., & Treadway, J. L. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm980264k · Cited by 100 · see citing works
Kidney: Its impact on glucose homeostasis and hormonal regulation
Mitrakou, A. (2011) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(11)70016-x · Cited by 99 · see citing works
Previs, S. F., Fatica, R. A., Chandramouli, V., Alexander, J. C., Brunengraber, H., & Landau, B. R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00271.2003 · Cited by 99 · see citing works
Self-citationTGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis
Yadav, H., Devalaraja, S., Chung, S. T., & Rane, S. G. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.764910 · Cited by 98 · see citing works
Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis
Petersen, K. F., Krššák, M., Navarro, V., Chandramouli, V., Hundal, R. S., Schumann, W. C., Landau, B. R., & Shulman, G. I. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.3.e529 · Cited by 96 · see citing works
Self-citationAckermans, M. T., Arias, A. M. P., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., & Romijn, J. A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.5.7383 · Cited by 94 · see citing works
Bisschop, P. H. L. T., Arias, A. M. P., Ackermans, M. T., Endert, E., Pijl, H., Kuipers, F., Meijer, A. J., Sauerwein, H. P., & Romijn, J. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.5.6573 · Cited by 93 · see citing works
Dock‐Nascimento, D. B., de Aguilar‐Nascimento, J. E., Faria, M. H. C. P., Caporossi, C., Slhessarenko, N., & Waitzberg, D. L. (2012) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607111422719 · Cited by 91 · see citing works
Erion, D. M., Park, H., & Lee, H. (2016) · BMB Reports · doi:10.5483/bmbrep.2016.49.3.268 · Cited by 87 · see citing works
Aquaglyceroporins: implications in adipose biology and obesity
Madeira, A., Moura, T. F., & Soveral, G. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1773-2 · Cited by 89 · see citing works
Basu, R., Schwenk, W. F., & Rizza, R. A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00549.2003 · Cited by 88 · see citing works
Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review
Chung, S. T., Chacko, S. K., Sunehag, A. L., & Haymond, M. W. (2015) · Diabetes · doi:10.2337/db15-0640 · Cited by 88 · see citing works
Corssmit, E. P. M., Romijn, J. A., & Sauerwein, H. P. (2001) · Metabolism · doi:10.1053/meta.2001.24195 · Cited by 87 · see citing works
Gómez-Valadés, A. G., Vidal‐Alabró, A., Molas, M., Boada, J., Bermúdez, J., Bartrons, R., & Perales, J. C. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.08.026 · Cited by 86 · see citing works
- Authors
- Landau, B. R., Wahren, J., Chandramouli, V, Schumann, W. C., Ekberg, K., & Kalhan, S. C.
- Affiliations
- Case Western Reserve University (US)
- Karolinska University Hospital (SE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1996-07-15
- Volume
- 98
- Issue
- 2
- Pages
- 378-385
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507441
- OpenAlex
- W2040750115
- Cited by
- 487
- References
- 56
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 20 · 2020: 18 · 2019: 14 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 21 · 2014: 17 · 2013: 16 · 2012: 28
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Riksbankens Jubileumsfond
- National Institutes of Health (11089, HD-11089)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-14507)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P-50-HD-11089, P50HD011089)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- gluconeogenesis, glucose production, fasting, deuterium tracer, blood glucose, glycerol, glycogenolysis, pyruvate, glucose-6-phosphate
- MeSH terms
- Adult, Blood Glucose, Chromatography, High Pressure Liquid, Deuterium, Fasting, Female, Gluconeogenesis, Glucose, Glycerol, Humans, Male, Radioisotope Dilution Technique, Time Factors, Xylose
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
