This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this book Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roden, M. Articles by Shulman, G. Search for Related Content PubMed PubMed Citation Articles by Roden, M. Articles by Shulman, G.

Nuclear Magnetic Resonance Studies of Hepatic Glucose Metabolism in Humans

Michael Roden^*, Kitt Falk Petersen and Geraldi Shulman^,

^* Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, A-1090, Austria
Department of Internal Medicine, Yale University, New Haven, Connecticut 06520
Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520

ABSTRACT

Nuclear magnetic resonance (NMR) spectroscopy has made noninvasive and repetitive measurements of human hepatic glycogen concentrations possible. Monitoring of liver glycogen in real-time mode has demonstrated that glycogen concentrations decrease linearly and that net hepatic glycogenolysis contributes only about 50 percent to glucose production during the early period of a fast. Following a mixed meal, hepatic glycogen represents approximately 20 percent of the ingested carbohydrates, while only about 10 percent of an intravenous glucose load is retained by the liver as glycogen. During mixed-meal ingestion, poorly controlled type 1 diabetic patients synthesize only about 30 percent of the glycogen stored in livers of nondiabetic humans studied under similar conditions. Reduced net glycogen synthesis can be improved but not normalized by short-term, intensified insulin treatment. A decreased increment in liver glycogen content following meals was also found in patients with maturity-onset diabetes of the young due to glucokinase mutations (MODY-2). In patients with poorly controlled type 2 diabetes, fasting hyperglycemia can be attributed mainly to increased rates of endogenous glucose production, which was found by ¹³C NMR to be due to increased rates of gluconeogenesis. Metformin treatment improved fasting hyperglycemia in these patients through a reduction in hepatic glucose production, which could be attributed to a decrease in gluconeogenesis. In conclusion, NMR spectroscopy has provided new insights into the pathogenesis of hyperglycemia in type 1, type 2, and MODY diabetes and offers the potential of providing new insights into the mechanism of action of novel antidabetic therapies.

This article has been cited by other articles:

				J. K. Hines, X. Chen, J. C. Nix, H. J. Fromm, and R. B. Honzatko Structures of Mammalian and Bacterial Fructose-1,6-bisphosphatase Reveal the Basis for Synergism in AMP/Fructose 2,6-Bisphosphate Inhibition J. Biol. Chem., December 7, 2007; 282(49): 36121 - 36131. [Abstract] [Full Text] [PDF]

				K. W. Sloop, A. D. Showalter, A. L. Cox, J. X. C. Cao, A. M. Siesky, H. Y. Zhang, A. R. Irizarry, S. F. Murray, S. L. Booten, E. A. Finger, et al. Specific Reduction of Hepatic Glucose 6-Phosphate Transporter-1 Ameliorates Diabetes while Avoiding Complications of Glycogen Storage Disease J. Biol. Chem., June 29, 2007; 282(26): 19113 - 19121. [Abstract] [Full Text] [PDF]

				D. B. Savage, K. F. Petersen, and G. I. Shulman Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance Physiol Rev, April 1, 2007; 87(2): 507 - 520. [Abstract] [Full Text] [PDF]

				G. Oz, E. R. Seaquist, A. Kumar, A. B. Criego, L. E. Benedict, J. P. Rao, P.-G. Henry, P.-F. Van De Moortele, and R. Gruetter Human brain glycogen content and metabolism: implications on its role in brain energy metabolism Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E946 - E951. [Abstract] [Full Text] [PDF]

				F. Andreelli, M. Foretz, C. Knauf, P. D. Cani, C. Perrin, M. A. Iglesias, B. Pillot, A. Bado, F. Tronche, G. Mithieux, et al. Liver Adenosine Monophosphate-Activated Kinase-{alpha}2 Catalytic Subunit Is a Key Target for the Control of Hepatic Glucose Production by Adiponectin and Leptin But Not Insulin Endocrinology, May 1, 2006; 147(5): 2432 - 2441. [Abstract] [Full Text] [PDF]

				W. Cao, Q. F. Collins, T. C. Becker, J. Robidoux, E. G. Lupo Jr., Y. Xiong, K. W. Daniel, L. Floering, and S. Collins p38 Mitogen-activated Protein Kinase Plays a Stimulatory Role in Hepatic Gluconeogenesis J. Biol. Chem., December 30, 2005; 280(52): 42731 - 42737. [Abstract] [Full Text] [PDF]

				P. B. Jacobson, T. W. von Geldern, L. Ohman, M. Osterland, J. Wang, B. Zinker, D. Wilcox, P. T. Nguyen, A. Mika, S. Fung, et al. Hepatic Glucocorticoid Receptor Antagonism Is Sufficient to Reduce Elevated Hepatic Glucose Output and Improve Glucose Control in Animal Models of Type 2 Diabetes J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 191 - 200. [Abstract] [Full Text] [PDF]

				D. B. Savage, K. F. Petersen, and G. I. Shulman Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation Hypertension, May 1, 2005; 45(5): 828 - 833. [Abstract] [Full Text] [PDF]

				L. Puljak, M. J Pagliassotti, Y. Wei, I. Qadri, V. Parameswara, V. Esser, J. G. Fitz, and G. Kilic Inhibition of cellular responses to insulin in a rat liver cell line. A role for PKC in insulin resistance J. Physiol., March 1, 2005; 563(2): 471 - 482. [Abstract] [Full Text] [PDF]

				P. Vuguin, E. Raab, B. Liu, N. Barzilai, and R. Simmons Hepatic Insulin Resistance Precedes the Development of Diabetes in a Model of Intrauterine Growth Retardation Diabetes, October 1, 2004; 53(10): 2617 - 2622. [Abstract] [Full Text] [PDF]

				A. B. Loucks and J. R. Thuma Luteinizing Hormone Pulsatility Is Disrupted at a Threshold of Energy Availability in Regularly Menstruating Women J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 297 - 311. [Abstract] [Full Text] [PDF]

				H. E Lebovitz Review: Type 2 diabetes: how far have we come? The British Journal of Diabetes & Vascular Disease, November 1, 2002; 2(6): 446 - 449. [Abstract] [PDF]

				D. S. Edgerton, S. Cardin, C. Pan, D. Neal, B. Farmer, M. Converse, and A. D. Cherrington. Effects of Insulin Deficiency or Excess on Hepatic Gluconeogenic Flux During Glycogenolytic Inhibition in the Conscious Dog Diabetes, November 1, 2002; 51(11): 3151 - 3162. [Abstract] [Full Text] [PDF]

				H. Stingl, W. J. Schnedl, M. Krssak, E. Bernroider, M. G. Bischof, T. Lahousen, G. Pacini, and M. Roden Reduction of Hepatic Glycogen Synthesis and Breakdown in Patients with Agenesis of the Dorsal Pancreas J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4678 - 4685. [Abstract] [Full Text] [PDF]

				Y. Sun, S. Liu, S. Ferguson, L. Wang, P. Klepcyk, J. S. Yun, and J. E. Friedman Phosphoenolpyruvate Carboxykinase Overexpression Selectively Attenuates Insulin Signaling and Hepatic Insulin Sensitivity in Transgenic Mice J. Biol. Chem., June 21, 2002; 277(26): 23301 - 23307. [Abstract] [Full Text] [PDF]