The “glycogen shunt” in exercising muscle: A role for glycogen in muscle energetics and fatigue
Shulman, R. G., Rothman, D. L.
Stimulated by recent 13C and 31P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the...
Sibson, N. R., Dhankhar, A., Mason, G. F., Behar, K. L., Rothman, D. L., Shulman, R. G.
The cerebral tricarboxylic acid (TCA) cycle rate and the rate of glutamine synthesis were measured in rats in vivo under normal physiological and hyperammonemic conditions using 13C NMR spectroscopy....
We recently analyzed experimental studies of mammalian muscle glycogen synthesis using metabolic control analysis and concluded that glycogen synthase (GSase) does not control the glycogenic flux but...
Hyder, F, Chase, J R, Behar, K L, Mason, G F, Siddeek, M, Rothman, D L, ...
NMR spectroscopy was used to test recent proposals that the additional energy required for brain activation is provided through nonoxidative glycolysis. Using localized NMR spectroscopic methods, the...
Price, T B, Perseghin, G, Duleba, A, Chen, W, Chase, J, Rothman, D L, ...
To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean,...
In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.
Shulman, R G, Bloch, G, Rothman, D L
The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent phosphorylation. Because of this regulation, GSase has generally been considered to control the rate of glycogen...
Rothman, D L, Magnusson, I, Cline, G, Gerard, D, Kahn, C R, Shulman, R G, ...
Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM)....
Nuclear magnetic resonance imaging and spectroscopy of human brain function.
Shulman, R G, Blamire, A M, Rothman, D L, McCarthy, G
The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have...
McCarthy, G, Blamire, A M, Rothman, D L, Gruetter, R, Shulman, R G
Nine subjects were studied by high-speed magnetic resonance imaging while performing language-based tasks. Subjects were asked either to repeat or to generate verbs associated with nouns read by an...
Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.
Rothman, D L, Petroff, O A, Behar, K L, Mattson, R H
Localized 1H NMR spectroscopy in conjunction with J editing was used to measure the concentration of gamma-aminobutyric acid (GABA) in the occipital lobe of four control human volunteers and four...
Localized 1H NMR measurement of glucose consumption in the human brain during visual stimulation.
Chen, W, Novotny, E J, Zhu, X H, Rothman, D L, Shulman, R G
Spatially localized 1H NMR spectroscopy has been applied to measure changes in brain glucose concentration during 8-Hz photic stimulation. NMR spectroscopic measurements were made in a 12-cm3 volume...
Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy.
Gruetter, R, Novotny, E J, Boulware, S D, Rothman, D L, Mason, G F, Shulman, G I, ...
Glucose is the main fuel for energy metabolism in the normal human brain. It is generally assumed that glucose transport into the brain is not rate-limiting for metabolism. Since brain glucose...
1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain.
Rothman, D L, Novotny, E J, Shulman, G I, Howseman, A M, Petroff, O A, Mason, G, ...
A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic...
1H NMR study of renal trimethylamine responses to dehydration and acute volume loading in man.
Avison, M J, Rothman, D L, Nixon, T W, Long, W S, Siegel, N J
We have used volume-localized 1H NMR spectroscopy to detect and measure changes in medullary trimethylamines (TMAs) in the human kidney in vivo. Localized water-suppressed 1H spectra were collected...
1H NMR visibility of mammalian glycogen in solution.
Zang, L H, Rothman, D L, Shulman, R G
High-resolution 1H NMR spectra of rabbit liver glycogen in 2H2O were obtained at 500 MHz, and several resonances were assigned by comparison with the chemical shifts of alpha-linked diglucose...
Surface coil localization of 31P NMR signals from orthotopic human kidney and liver.
Jue, T, Rothman, D L, Lohman, J A, Hughes, E W, Hanstock, C C, Shulman, R G
By incorporating the hyperbolic secant inversion pulses with the image-selected in vivo spectroscopy localization technique and by applying a gradient-echo imaging method, we have selected only the...
Detection of human muscle glycogen by natural abundance 13C NMR.
Avison, M J, Rothman, D L, Nadel, E, Shulman, R G
Natural abundance 13C nuclear magnetic resonance spectroscopy was used to detect signals from glycogen in the human gastrocnemius muscle. The reproducibility of the measurement was demonstrated, and...
Spatially localized 1H NMR spectra of metabolites in the human brain.
Hanstock, C C, Rothman, D L, Prichard, J W, Jue, T, Shulman, R G
Using a surface coil, we have obtained 1H NMR spectra from metabolites in the human brain. Localization was achieved by combining depth pulses with image-selected in vivo spectroscopy magnetic field...
Intracellular pH in human skeletal muscle by 1H NMR.
Pan, J W, Hamm, J R, Rothman, D L, Shulman, R G
We report here the in vivo observation of the imidazole protons (C-2 and C-4) of carnosine (beta-Ala-His) by 1H NMR at 4.7 T in human skeletal muscle. The relationship between the pH and chemical...
Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle.
Jue, T, Rothman, D L, Tavitian, B A, Shulman, R G
Optimizing the surface-coil design and spectral-acquisition parameters has lead to the observation of the 13C NMR natural abundance glycogen signal in man at 2.1 T. Both the human muscle and hepatic...
Direct observation of glycogen synthesis in human muscle with 13C NMR.
Jue, T, Rothman, D L, Shulman, G I, Tavitian, B A, DeFronzo, R A, Shulman, R G
On the basis of previous indirect measurements, skeletal muscle has been implicated as the major site of glucose uptake and it has been suggested that muscle glycogen formation is the dominant...
Hwang, J H, Perseghin, G, Rothman, D L, Cline, G W, Magnusson, I, Petersen, K F, ...
Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using 13C nuclear magnetic resonance spectroscopy...
Cline, G W, Rothman, D L, Magnusson, I, Katz, L D, Shulman, G I
To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear...
Behar, K L, Rothman, D L, Shulman, R G, Petroff, O A, Prichard, J W
1H NMR was used to monitor lactate production and clearance during hypoxemia and recovery in the rabbit brain at the relatively low magnetic-field strength of 1.89 T. An array of conventional...
Homonuclear 1H double-resonance difference spectroscopy of the rat brain in vivo.
Rothman, D L, Behar, K L, Hetherington, H P, Shulman, R G
We have used 1H homonuclear double-resonance difference spectroscopy at 360.13 MHz to resolve specific metabolite resonances in the brains of intact rats. Metabolite resonances resolved include...
Rothman, D L, Behar, K L, Hetherington, H P, Den Hollander, J A, Bendall, M R, Petroff, O A, ...
We have used (13C)-1H NMR spectroscopy at 360.13 MHz to resolve the 13C coupled proton resonance of glutamate and lactate in the rat brain in vivo. The time required for the 13C fractional enrichment...
Mechanism of liver glycogen repletion in vivo by nuclear magnetic resonance spectroscopy.
Shulman, G I, Rothman, D L, Smith, D, Johnson, C M, Blair, J B, Shulman, R G, ...
In order to quantitate the pathways by which liver glycogen is repleted, we administered [1-13C]glucose by gavage into awake 24-h fasted rats and examined the labeling pattern of 13C in hepatic...
Shulman, G I, Rossetti, L, Rothman, D L, Blair, J B, Smith, D
In order to directly determine the amount of label exchange that occurs in the tricarboxylic cycle from labeled alanine and lactate after the ingestion of a glucose load [1-13C]glucose was...
Rothman, D L, Shulman, R G, Shulman, G I
To assess the rate-limiting step in muscle glycogen synthesis in non-insulin-dependent diabetes mellitus (NIDDM), the concentration of glucose-6-phosphate (G6P) was measured by 31P nuclear magnetic...
Magnusson, I, Rothman, D L, Katz, L D, Shulman, R G, Shulman, G I
To quantitate hepatic glycogenolysis, liver glycogen concentration was measured with 13C nuclear magnetic resonance spectroscopy in seven type II diabetic and five control subjects during 23 h of...
Taylor, R, Magnusson, I, Rothman, D L, Cline, G W, Caumo, A, Cobelli, C, ...
Despite extensive recent studies, understanding of the normal postprandial processes underlying immediate storage of substrate and maintenance of glucose homeostasis in humans after a mixed meal has...
Roden, M, Perseghin, G, Petersen, K F, Hwang, J H, Cline, G W, Gerow, K, ...
To determine the respective roles of insulin and glucagon for hepatic glycogen synthesis and turnover, hyperglycemic clamps were performed with somatostatin [0.1 micrograms/(kg.min)] in healthy young...
Mechanism of free fatty acid-induced insulin resistance in humans.
Roden, M, Price, T B, Perseghin, G, Petersen, K F, Rothman, D L, Cline, G W, ...
To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P...
Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.
Velho, G, Petersen, K F, Perseghin, G, Hwang, J H, Rothman, D L, Pueyo, M E, ...
All glucokinase gene mutations identified to date have been localized to exons that are common to the pancreatic and hepatic isoforms of the enzyme. While impaired insulin secretion has been observed...
Cline, G W, Magnusson, I, Rothman, D L, Petersen, K F, Laurent, D, Shulman, G I
To determine the mechanism of impaired insulin-stimulated muscle glycogen metabolism in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM), we used 13C-NMR spectroscopy to...
Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans.
Petersen, K F, Laurent, D, Rothman, D L, Cline, G W, Shulman, G I
13C NMR spectroscopy was used to assess flux rates of hepatic glycogen synthase and phosphorylase in overnight-fasted subjects under one of four hypoglucagonemic conditions: protocol I, hyperglycemic...
The “glycogen shunt” in exercising muscle: A role for glycogen in muscle energetics and fatigue
Shulman, R. G., Rothman, D. L.
Stimulated by recent 13C and 31P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the...
Sibson, N. R., Dhankhar, A., Mason, G. F., Behar, K. L., Rothman, D. L., Shulman, R. G.
The cerebral tricarboxylic acid (TCA) cycle rate and the rate of glutamine synthesis were measured in rats in vivo under normal physiological and hyperammonemic conditions using 13C NMR spectroscopy....
We recently analyzed experimental studies of mammalian muscle glycogen synthesis using metabolic control analysis and concluded that glycogen synthase (GSase) does not control the glycogenic flux but...
Hyder, F, Chase, J R, Behar, K L, Mason, G F, Siddeek, M, Rothman, D L, ...
NMR spectroscopy was used to test recent proposals that the additional energy required for brain activation is provided through nonoxidative glycolysis. Using localized NMR spectroscopic methods, the...
Price, T B, Perseghin, G, Duleba, A, Chen, W, Chase, J, Rothman, D L, ...
To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean,...
In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.
Shulman, R G, Bloch, G, Rothman, D L
The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent phosphorylation. Because of this regulation, GSase has generally been considered to control the rate of glycogen...
Rothman, D L, Magnusson, I, Cline, G, Gerard, D, Kahn, C R, Shulman, R G, ...
Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM)....
Nuclear magnetic resonance imaging and spectroscopy of human brain function.
Shulman, R G, Blamire, A M, Rothman, D L, McCarthy, G
The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have...
McCarthy, G, Blamire, A M, Rothman, D L, Gruetter, R, Shulman, R G
Nine subjects were studied by high-speed magnetic resonance imaging while performing language-based tasks. Subjects were asked either to repeat or to generate verbs associated with nouns read by an...
Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.
Rothman, D L, Petroff, O A, Behar, K L, Mattson, R H
Localized 1H NMR spectroscopy in conjunction with J editing was used to measure the concentration of gamma-aminobutyric acid (GABA) in the occipital lobe of four control human volunteers and four...
Localized 1H NMR measurement of glucose consumption in the human brain during visual stimulation.
Chen, W, Novotny, E J, Zhu, X H, Rothman, D L, Shulman, R G
Spatially localized 1H NMR spectroscopy has been applied to measure changes in brain glucose concentration during 8-Hz photic stimulation. NMR spectroscopic measurements were made in a 12-cm3 volume...
Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy.
Gruetter, R, Novotny, E J, Boulware, S D, Rothman, D L, Mason, G F, Shulman, G I, ...
Glucose is the main fuel for energy metabolism in the normal human brain. It is generally assumed that glucose transport into the brain is not rate-limiting for metabolism. Since brain glucose...
1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain.
Rothman, D L, Novotny, E J, Shulman, G I, Howseman, A M, Petroff, O A, Mason, G, ...
A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic...
1H NMR study of renal trimethylamine responses to dehydration and acute volume loading in man.
Avison, M J, Rothman, D L, Nixon, T W, Long, W S, Siegel, N J
We have used volume-localized 1H NMR spectroscopy to detect and measure changes in medullary trimethylamines (TMAs) in the human kidney in vivo. Localized water-suppressed 1H spectra were collected...
1H NMR visibility of mammalian glycogen in solution.
Zang, L H, Rothman, D L, Shulman, R G
High-resolution 1H NMR spectra of rabbit liver glycogen in 2H2O were obtained at 500 MHz, and several resonances were assigned by comparison with the chemical shifts of alpha-linked diglucose...
Surface coil localization of 31P NMR signals from orthotopic human kidney and liver.
Jue, T, Rothman, D L, Lohman, J A, Hughes, E W, Hanstock, C C, Shulman, R G
By incorporating the hyperbolic secant inversion pulses with the image-selected in vivo spectroscopy localization technique and by applying a gradient-echo imaging method, we have selected only the...
Detection of human muscle glycogen by natural abundance 13C NMR.
Avison, M J, Rothman, D L, Nadel, E, Shulman, R G
Natural abundance 13C nuclear magnetic resonance spectroscopy was used to detect signals from glycogen in the human gastrocnemius muscle. The reproducibility of the measurement was demonstrated, and...
Spatially localized 1H NMR spectra of metabolites in the human brain.
Hanstock, C C, Rothman, D L, Prichard, J W, Jue, T, Shulman, R G
Using a surface coil, we have obtained 1H NMR spectra from metabolites in the human brain. Localization was achieved by combining depth pulses with image-selected in vivo spectroscopy magnetic field...
Intracellular pH in human skeletal muscle by 1H NMR.
Pan, J W, Hamm, J R, Rothman, D L, Shulman, R G
We report here the in vivo observation of the imidazole protons (C-2 and C-4) of carnosine (beta-Ala-His) by 1H NMR at 4.7 T in human skeletal muscle. The relationship between the pH and chemical...
Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle.
Jue, T, Rothman, D L, Tavitian, B A, Shulman, R G
Optimizing the surface-coil design and spectral-acquisition parameters has lead to the observation of the 13C NMR natural abundance glycogen signal in man at 2.1 T. Both the human muscle and hepatic...
Direct observation of glycogen synthesis in human muscle with 13C NMR.
Jue, T, Rothman, D L, Shulman, G I, Tavitian, B A, DeFronzo, R A, Shulman, R G
On the basis of previous indirect measurements, skeletal muscle has been implicated as the major site of glucose uptake and it has been suggested that muscle glycogen formation is the dominant...
Hwang, J H, Perseghin, G, Rothman, D L, Cline, G W, Magnusson, I, Petersen, K F, ...
Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using 13C nuclear magnetic resonance spectroscopy...
Cline, G W, Rothman, D L, Magnusson, I, Katz, L D, Shulman, G I
To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear...
Behar, K L, Rothman, D L, Shulman, R G, Petroff, O A, Prichard, J W
1H NMR was used to monitor lactate production and clearance during hypoxemia and recovery in the rabbit brain at the relatively low magnetic-field strength of 1.89 T. An array of conventional...
Homonuclear 1H double-resonance difference spectroscopy of the rat brain in vivo.
Rothman, D L, Behar, K L, Hetherington, H P, Shulman, R G
We have used 1H homonuclear double-resonance difference spectroscopy at 360.13 MHz to resolve specific metabolite resonances in the brains of intact rats. Metabolite resonances resolved include...
Rothman, D L, Behar, K L, Hetherington, H P, Den Hollander, J A, Bendall, M R, Petroff, O A, ...
We have used (13C)-1H NMR spectroscopy at 360.13 MHz to resolve the 13C coupled proton resonance of glutamate and lactate in the rat brain in vivo. The time required for the 13C fractional enrichment...
Mechanism of liver glycogen repletion in vivo by nuclear magnetic resonance spectroscopy.
Shulman, G I, Rothman, D L, Smith, D, Johnson, C M, Blair, J B, Shulman, R G, ...
In order to quantitate the pathways by which liver glycogen is repleted, we administered [1-13C]glucose by gavage into awake 24-h fasted rats and examined the labeling pattern of 13C in hepatic...
Shulman, G I, Rossetti, L, Rothman, D L, Blair, J B, Smith, D
In order to directly determine the amount of label exchange that occurs in the tricarboxylic cycle from labeled alanine and lactate after the ingestion of a glucose load [1-13C]glucose was...
Rothman, D L, Shulman, R G, Shulman, G I
To assess the rate-limiting step in muscle glycogen synthesis in non-insulin-dependent diabetes mellitus (NIDDM), the concent