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Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications is the first comprehensive book for non-physicists that addresses the emerging and exciting technique of magnetic resonance spectroscopy. Divided into three sections, this book provides coverage of the key areas of concern for researchers. The first, on how MRS is acquired, provides a comprehensive overview of the techniques, analysis, and pitfalls encountered in MRS; the second, on what can be seen by MRS, provides essential background physiology and biochemistry on the major metabolites studied; the final sections, on why MRS is used, constitutes a detailed guide to the major clinical and scientific uses of MRS, the current state of teh art, and recent innovations. Magnetic Resonance Spectroscopy will become the essential guide for people new to the technique and give those more familiar with MRS a new perspective. © 2014 Elsevier Inc. All rights reserved.

We propose a dynamical model for the erosive growth of a channel in a granular medium driven by subsurface water flow. The model is inferred from experimental data acquired with a laser-aided imaging technique. The evolution equation for transverse sections of a channel has the form of a non-locally driven Burgers equation. With fixed coefficients this equation admits an asymptotic similarity solution. Ratios of the granular transport coefficients can therefore be extracted from the shape of channels that have evolved in steady driving conditions., 5 pages, 4 figures

The aims of this study were twofold: (i) to determine quantitatively the contribution of glutamate/glutamine cycling to total astrocyte/neuron substrate trafficking for the replenishment of neurotransmitter glutamate; and (ii) to determine the relative contributions of anaplerotic flux and glutamate/glutamine cycling to total glutamine synthesis. In this work in vivo and in vitro (13)C NMR spectroscopy were used, with a [2-(13)C]glucose or [5-(13)C]glucose infusion, to determine the rates of glutamate/glutamine cycling, de novo glutamine synthesis via anaplerosis, and the neuronal and astrocytic tricarboxylic acid cycles in the rat cerebral cortex. The rate of glutamate/glutamine cycling measured in this study is compared with that determined from re-analysis of (13)C NMR data acquired during a [1-(13)C]glucose infusion. The excellent agreement between these rates supports the hypothesis that glutamate/glutamine cycling is a major metabolic flux ( approximately 0.20 micromol/min/g) in the cerebral cortex of anesthetized rats and the predominant pathway of astrocyte/neuron trafficking of neurotransmitter glutamate precursors. Under normoammonemic conditions anaplerosis was found to comprise 19-26% of the total glutamine synthesis, whilst this fraction increased significantly during hyperammonemia ( approximately 32%). These findings indicate that anaplerotic glutamine synthesis is coupled to nitrogen removal from the brain (ammonia detoxification) under hyperammonemic conditions.

The aims of this study were twofold: (i) to determine quantitatively the contribution of glutamate/glutamine cycling to total astrocyte/neuron substrate trafficking for the replenishment of neurotransmitter glutamate; and (ii) to determine the relative contributions of anaplerotic flux and glutamate/glutamine cycling to total glutamine synthesis. In this work in vivo and in vitro 13C NMR spectroscopy were used, with a [2-13C]glucose or [5-13C]glucose infusion, to determine the rates of glutamate/glutamine cycling, de novo glutamine synthesis via anaplerosis, and the neuronal and astrocytic tricarboxylic acid cycles in the rat cerebral cortex. The rate of glutamate/glutamine cycling measured in this study is compared with that determined from re-analysis of 13C NMR data acquired during a [1-13C]glucose infusion. The excellent agreement between these rates supports the hypothesis that glutamate/glutamine cycling is a major metabolic flux (∼0.20 μmol/min/g) in the cerebral cortex of anesthetized rats and the predominant pathway of astrocyte/neuron trafficking of neurotransmitter glutamate precursors. Under normoammonemic conditions anaplerosis was found to comprise 19-26% of the total glutamine synthesis, whilst this fraction increased significantly during hyperammonemia (∼32%). These findings indicate that anaplerotic glutamine synthesis is coupled to nitrogen removal from the brain (ammonia detoxification) under hyperammonemic conditions.

The growth in popularity of so-called "anti-aging" medicine challenges physicians to examine their attitudes about aging. Does one define aging as a predisposition to pathology or as part of the life cycle? Is longevity without the chronic diseases associated with aging a realistic goal? Anti-aging modalities being prescribed by some practitioners include hormone replacement therapies, vitamin and mineral supplements, diet, and exercise. Although diet, exercise, and some vitamin and mineral supplements are well-recognized as preventive measures, unproven hormone, mega-vitamin, and herbal therapies are controversial. Both the patient and the physician bring biases and values to the discussion of anti-aging medicine, and that combination will influence the treatment decisions.

A previously unpublished paper by a dying psychotherapist describes the therapeutic use of the ensuing grief reactions of five patients to his terminal illness to help them deal with the effects of their previous losses, deprivations, and abandonments. Follow-up interviews with these patients and their subsequent psychotherapists shed light on the efficacy of such therapeutic efforts, the character of the communication of the terminal illness, the transference and countertransference reactions that interfered with the inevitable separation, and conclusions by previous authors regarding patients' reactions to the deaths of their therapists.

The compromised human newborn frequently presents with overwhelming feeding problems which lead to inadequate intake. These problems may affect the development of the small intestine, especially mucosal barrier function, leading to increased infections and susceptibility to allergens. To study this, an animal model was established using neonatal rabbits deprived of nutrients from birth until 72 h. Mucosal barrier function was compared in deprived and control (naturally fed 72-h-old animals) rabbits by measuring immunoreactive bovine serum albumin in serum 4 h after intragastric infusion of crystalline bovine serum albumin (200 mg/100 g body weight). Trypsin activity was measured in rinse fluid obtained from the small intestine. Representative sections of jejunum from control and experimental animals were formalin fixed and stained with hematoxylin and eosin for morphologic comparison. Following the bovine serum albumin feeding, a significantly increased serum immunoreactive bovine serum albumin and significantly decreased trypsin-like activity of the small intestinal rinse fluid was noted in starved animals compared to controls. In addition, the enterocytes of malnourished animals were more cuboidal and contained fewer and smaller supranuclear granules on microscopic examination than the enterocytes of controls. This study suggests that short-term starvation in newborns affects mucosal barrier function. Acute starvation may place newborns at increased risk for infections and allergic disease.

The difference between 1H nuclear magnetic resonance (NMR) spectra obtained from the human brain during euglycemia and during hyperglycemia is depicted as well-resolved glucose peaks. The time course of these brain glucose changes during a rapid increase in plasma glucose was measured in four healthy subjects, aged 1822 years, in five studies. Results demonstrated a significant lag in the rise of glucose with respect to plasma glucose. The fit of the integrated symmetric Michaelis-Menten model to the time course of relative glucose signals yielded an estimated plasma glucose concentration for half maximal transport, K(t), of 4.8 ± 2.4 mM (mean ± SD), a maximal transport rate, T(max), of 0.80 ± 0.45 μmol g-1 min-1], and a cerebral metabolic glucose consumption rate (CMR)(glc) of 0.32 ± 0.16 μmol g-10 min-1. Assuming cerebral glucose concentration to be 1.0 μmol/g at euglycemia as measured by 13C NMR, the fit of the same model to the time course of brain glucose concentrations resulted in K(t) = 3.9 ± 0.82 mM, T(max) = 1.16 ± 0.29 μmol g-1 min-1, and CMR(glc) = 0.35 ± 0.10 μmol g-1 min-1. In both cases, the resulting time course equaled that predicted from the determination of the steady-state glucose concentration by 13C NMR spectroscopy within the experimental scatter. The agreement between the two methods of determining transport kinetics suggests that glucose is distributed throughout the entire aqueous phase of the human brain, implying substantial intracellular concentration.

The difference between 1H NMR spectra obtained during eu- and hyperglycemia exhibited well-resolved glucose peaks between 3 and 4 ppm as demonstrated by comparison with solution spectra. Estimated increases were consistent with recent 13C NMR quantitations of intracerebral glucose. Difference spectra were measured in 36-ml volumes from the human brain every 3 min.

13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min-1 g-1 (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α- ketoglutarate/glutamate exchange was 57 ± 26 μmol min-1 g-1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min-1 g-1 (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min-1 g-1; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the brain oxygen consumption was estimated to be 2.14 ± 0.48 μmol min-1 g-1 (5.07 ± 1.14 ml 100 g-1 min-1; n = 4), and the rate of brain glucose consumption was calculated to be 0.37 ± 0.08 μmol min-1 g-1 (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.

Cerebral metabolism of D[1-13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1-13C]glucose in four healthy subjects. The use of three-dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution were sufficient to allow 4 min of time-resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution. [4-13C]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3- 13C]glutamate clearly lagged behind that of [4-13C]glutamate and peaked at t = 110-140 min. Multiplets due to homonuclear 13C-13C coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spectra acquired between 120 and 180 min yielded a 13C isotopic fraction at C4 glutamate of 27 ± 2% (n = 4), which was slightly less than one-half the enrichment of the C1 position of plasma glucose (63 ± 1%), p < 0.05. By comparison with an external standard the total amount of [4-13C]glutamate was directly quantified to be 2.4 ± 0.1 μmol/ml-brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 ± 0.7 μmol/ml, which agrees with previous estimates of total brain glutamate concentrations. The agreement suggests that essentially all of the brain glutamate is derived from glucose in healthy human brain.

Natural abundance 13C NMR spectra obtained from 144-cm3 volumes in the human brain contained well-resolved resonances of myo-inositol after 60 min of data accumulation. A mean concentration of 7.2 +/- 0.5 mumol/g (+/- SE, n = 7) was calculated from the comparison with phantoms. 13C NMR spectroscopy thus provides a complementary role in the quantitation of metabolites also observed in the crowded 1H spectrum.

The natural abundance 13C NMR intensity of the glycogen C1 resonance was measured in the surgically exposed liver of rabbits in vivo (n = 17) by integration from 98 to 104 ppm and compared double blindedly to the subsequent biochemical measurement. Coil loading was measured each time from a reference sphere at the coil center and the NMR intensity was normalized accordingly. For quantification, the normalized NMR intensity was calibrated using aqueous glycogen solutions ranging from 110 to 1100 μmol glucosyl units/g (n = 14). An in vivo range from 110 to 800 μmol glucosyl units/g wet weight was measured with a highly linear correlation with concentration (r = 0.85, P < 0.001). The in vivo NMR concentration was 0.95 ± 0.05 (mean ± standard error, n = 17) of the concomitant enzymatic measurement of glycogen content. We conclude that the 13C NMR signal of liver glycogen C1 is essentially 100% visible in vivo and that natural abundance 13C NMR spectroscopy can provide reliable noninvasive estimates of in vivo glycogen content over the physiological range of liver glycogen concentrations when using adequate localization and integration procedures.

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 experimenter while magnetic resonance images were obtained of the left inferior frontal lobe. The echo-planar imaging sequence was used with a gradient echo time of 70 ms to give an apparent transverse relaxation time weighting (T2* that is sensitive to local hemoglobin levels. Images were acquired every 3 s (repetition time) in series of 32. In plane resolution was 6 x 4.5 mm and slice thickness was 10 mm. An increase in signal accompanied performance of the tasks, with significantly more activation for verb generation than for repeating. The activation effect occurred within 3 s after task onset and could be observed in single images from individual subjects. The primary focus of activation appeared in gray matter along a sulcus anterior to the lateral sulcus that included the anterior insula, Brodmann's area 47, and extending to area 10. Little or no activation of this region was found for a passive listening, covert generation, or mouth-movement control tasks. Significant activation was also found for a homologous region in the right frontal cortex but not for control regions in calcarine cortex. These results are consistent with prior studies that have used positron emission tomography imaging with 15O-labeled water as a blood flow tracer.

Angle resolved 2-D PIV measurements were taken of the flow inside an in-line Silverson 150/250 high shear mixer, facilitated by a custom built transparent poly methyl methacrylate mixing head. Water was used as the working fluid in the turbulent regime (120,000 < Re < 420,000) and measurements were taken in a field of view encompassing one quarter of the whole mixing head. The effect of the presence of an additional externally driven flow from a pump, and back pressure using an outlet control valve, were examined. The results show that the dominant flow pattern can either be radial or tangential with the former being driven by the external flow at high flow rates and the latter at increasing rotor speeds. Increasing the back pressure promoted tangential flow. Detailed measurements were made of the influence of these parameters upon the mixer flow pattern and calculation of flow number from 2-D PIV data; the latter are strongly influenced by the geometry of the mixer and pipework.

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 nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.

The mechanism of insulin resistance in obesity was examined in ten obese (BMI 33 +/- 1 kg/m2) and nine lean (BMI 22 +/- 1 kg/m2) Caucasian women during a hyperglycemic-hyperinsulinemic clamp using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy to measure rates of muscle glycogen synthesis and intramuscular glucose-6-phosphate (G-6-P) concentrations. Under similar steady-state plasma concentrations of glucose (approximately 11 mmol/l) and insulin (approximately 340 pmol/l), rates of muscle glycogen synthesis were reduced approximately 70% in the obese subjects (52 +/- 8 micromol/[l muscle-min]) as compared with the rates in the lean subjects (176 +/- 22 micromol/[l muscle-min]; P < 0.0001). Basal concentrations of intramuscular G-6-P were similar in the obese and lean subjects; but during the clamp, G-6-P failed to increase in the obese group (deltaG-6-P obese 0.044 +/- 0.011 vs. lean 0.117 +/- 0.011 mmol/l muscle; P < 0.001), reflecting decreased muscle glucose transport and/or phosphorylation activity. We conclude that insulin resistance in obesity can be mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis due to a defect in glucose transport and/or phosphorylation activity.

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 in glucokinase-deficient subjects the consequences of this mutation on hepatic glucose metabolism remain unknown. To examine this question hepatic glycogen concentration was measured in seven glucokinase-deficient subjects with normal glycosylated hemoglobin and 12 control subjects using 13C nuclear magnetic spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Average fasting hepatic glycogen content was similar in glucokinase-deficient and control subjects (279+/-20 vs 284+/-14 mM; mean+/-SEM), and increased in both groups after the meals with a continuous pattern throughout the day. However, the net increment in hepatic glycogen content after each meal was 30-60% lower in glucokinase-deficient than in the control subjects (breakfast, 46% lower, P < 0.02; lunch, 62% lower, P = 0.002; dinner; 30% lower, P = 0.04). The net increment over basal values 4 h after dinner was 105 +/-18 mM in glucokinase-deficient and 148+/-11 mM in control subjects (P = 0.04). In the 4 h after breakfast, flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was higher in glucokinase-deficient than in control subjects (50+/-2% vs 34+/-5%; P = 0.038). In conclusion glucokinase-deficient subjects have decreased net accumulation of hepatic glycogen and relatively augmented hepatic gluconeogenesis after meals. These results suggest that in addition to the altered beta cell function, abnormalities in liver glycogen metabolism play an important role in the pathogenesis of hyperglycemia in patients with glucokinase-deficient maturity onset diabetes of young.

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, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to approximately 25% of resting concentration. After approximately 20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 +/- 1.3 mM/hr and CON, 15.8 +/- 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 +/- 0.5 mM/hr and CON, 2.9 +/- 0.2 mM/hr; (P < or = 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen-depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal.

Background. Insulin resistance in the offspring of parents with non- insulin-dependent diabetes mellitus (NIDDM) is the best predictor of development of the disease and probably plays an important part in its pathogenesis. We studied the mechanism and degree to which exercise training improves insulin sensitivity in these subjects. Methods. Ten adult children of parents with NIDDM and eight normal subjects were studied before starting an aerobic exercise-training program, after one session of exercise, and after six weeks of exercise. Insulin sensitivity was measured by the hyperglycemic-hyperinsulinemic clamp technique combined with indirect calorimetry, and the rate of glycogen synthesis in muscle and the intramuscular glucose-6-phosphate concentration were measured by carbon-13 and phosphorus-31 nuclear magnetic resonance spectroscopy, respectively. Results. During the base-line study, the mean (±SE) rate of muscle glycogen synthesis was 63±9 percent lower in the offspring of diabetic parents than in the normal subjects (P

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 during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units-->-->glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia.

Single-voxel proton MRS can be obtained with inversion-based, echo-based, and hybrid methods. Yet, standard localization methods do not guarantee quality. Therefore, knowing basic principles, such as influence factors on both volume definition and spectral quality, including radiofrequency pulses, gradients, chemical shift errors, water-suppression techniques, and outer volume suppression, is very important. In this chapter, we describe factors affecting performance of short echo-time single-voxel proton spectroscopy and currently available localization methods for 1H MRS.

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 men under conditions of: (I) basal fasting) portal vein insulinemia-hypoglucagonemia, (II) basal portal vein insulinemia-basal glucagonemia, and (III) basal peripheral insulinemia-hypoglucagonemia. Synthetic rates, pathway (direct versus indirect) contributions, and percent turnover of hepatic glycogen were assessed by in vivo 13C nuclear magnetic resonance spectroscopy during [1-13C]glucose infusion followed by a natural abundance glucose chase in conjunction with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. In the presence of hyperglycemia (10.4 +/- 0.1 mM) and basal portal vein insulinemia (192 +/- 6 pM), suppression of glucagon secretion (plasma glucagon, I:31 +/- 4, II: 63 +/- 8 pg/ml) doubled the hepatic accumulation of glycogen (Vsyn) compared with conditions of basal glucagonemia [I: 0.40 +/- 0.06, II: 0.19 +/- 0.03 mumol/(liter.min): P < 0.0025]. Glycogen turnover was markedly reduced (I: 19 +/- 7%, II: 69 +/- 12%; P < 0.005), so that net rate of glycogen synthesis increased approximately fivefold (P < 0.001) by inhibition of glucagon secretion. The relative contribution of gluconeogenesis (indirect pathway) to glycogen synthesis was lower during hypoglucagonemia (42 +/- 6%) than during basal glucagonemia (54 +/- 5%; P < 0.005). Under conditions of basal peripheral insulinemia (54 +/- 2 pM) and hypoglucagonemia (III) there was negligible hepatic glycogen synthesis and turnover. In conclusion, small changes in portal vein concentrations of insulin and glucagon independently affect hepatic glycogen synthesis and turnover. Inhibition of glucagon secretion under conditions of hyperglycemia and basal concentrations of insulin results in: (a) twofold increase in rate of hepatic glycogen synthesis, (b) reduction of glycogen turnover by approximately 73%, and (c) augmented percent contribution of the direct pathway to glycogen synthesis compared with conditions of basal glucagonemia.