Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O.

The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 micromol MG was quantitatively recovered from a 2-h urine collection by ether extraction and a 125 micromol portion was directly analyzed by 2H NMR. The glucuronide 2H-signals were fully resolved and their relative intensities matched those of the monoacetone glucose derivative. The pharmacokinetics and yields of urinary MG after ingestion of 400 mg peppermint oil as either gelatin or enteric-coated capsules 1 h before breakfast were quantified in five healthy subjects. Gelatin capsules yielded 197 +/- 81 micromol of MG from the initial 2-h urine collection while enteric-coated capsules gave 238 +/- 84 micromol MG from the 2- to 4-h urine collection.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Quantification of hepatic transaldolase exchange activity and its effects on tracer measurements of indirect pathway flux in humans.

Exchange of hepatic glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate via transaldolase modifies hepatic G6P enrichment from glucose or gluconeogenic tracers. Transaldolase exchange was quantified in five healthy, fed subjects following an oral bolus of [1,2,3-(13)C(3)]glycerol (25-30 mg/kg) and paracetamol (10-12 mg/kg). (13)C Isotopomers of hepatic G6P were quantified by (13)C NMR spectroscopy of urinary glucuronide. [1,2,3-(13)C(3)]- and [4,5,6-(13)C(3)]glucuronide isotopomers, representing the conversion of [1,2,3-(13)C(3)]glycerol to G6P via dihydroxyacetone phosphate, were resolved from [1,2-(13)C(2)]- and [5,6-(13)C(2)]glucuronide (13)C-isotopomers, derived from metabolism of [1,2,3-(13)C(3)]glycerol via pyruvate and phosphoenolpyruvate. Enrichment of [1,2,3-(13)C(3)]glucuronide was significantly less than that of [4,5,6-(13)C(3)]glucuronide (1.30 +/- 0.57% versus 1.67 +/- 0.42%, P < 0.05). Also, [1,2-(13)C(2)]glucuronide enrichment was significantly less than that of [5,6-(13)C(2)]glucuronide (0.28 +/- 0.08% versus 0.36 +/- 0.03%, P < 0.05). Transaldolase and triose phosphate isomerase exchange activities were estimated by applying the (13)C-isotopomer data to a model of hepatic sugar phosphate metabolism. Triose phosphate isomerase exchange was approximately 99% complete and did not contribute significantly to the unequal (13)C-isotopomer distributions of the glucuronide triose halves. Instead, this was attributable to 25 +/- 23% of hepatic G6P flux undergoing transaldolase exchange. This results in substantial overestimates of indirect pathway contributions to hepatic glycogen synthesis with tracers such as [5-(3)H]glucose and (2)H(2)O.     

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment

The contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after ²H₂O ingestion by Bayesian analysis of the position 2 and 5 ²H‐NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 ± 1.0 kg/m²; fasting glucose = 4.7 ± 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 ± 0.7 kg/m²; fasting glucose = 7.1 ± 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% ± 5%. This uncertainty was associated with a mean signal‐to‐noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% ± 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% ± 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% ± 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia. Magn Reson Med 60:517–523, 2008. © 2008 Wiley‐Liss, Inc.     

Quantifying endogenous glucose production and contributing source fluxes from a single 2H NMR spectrum

Endogenous glucose production (EGP), gluconeogenic and glycogenolytic fluxes by analysis of a single ²H‐NMR spectrum is demonstrated with 6‐hr and 24‐hr fasted rats. Animals were administered [1‐²H, 1‐¹³C]glucose, a novel tracer of glucose turnover, and ²H₂O. Plasma glucose enrichment from both tracers was quantified by ²H‐NMR analysis of monoacetone glucose. The 6‐hr fasted group (n = 7) had EGP rates of 95.6 ± 13.3 μmol/kg/min, where 56.2 ± 7.9 μmol/kg/min were derived from PEP; 12.1 ± 2.1 μmol/kg/min from glycerol, and 32.1 ± 4.9 μmol/kg/min from glycogen. The 24‐hr fasted group (n = 7) had significantly lower EGP rates (52.8 ± 7.2 μmol/kg/min, P = 0.004 vs. 6 hr) mediated by a significantly reduced contribution from glycogen (4.7 ± 5.9 μmol/kg/min, P = 0.02 vs. 6 hr) while PEP and glycerol contributions were not significantly different (39.5 ± 3.9 and 8.5 ± 1.2 μmol/kg/min, respectively). These estimates agree with previous assays of EGP fluxes in fasted rats obtained by multinuclear NMR analyses of plasma glucose enrichment from ²H₂O and ¹³C‐glucose tracers. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Effect of sucrose and caffeine ingestion on performance of prolonged strenuous running

To investigate the effect of sucrose or caffeine ingestion on the performance of prolonged running, five male distance runners attending senior high school (15.6 yrs) carried out running on a treadmill at an intensity corresponding to the individuals' 80% VO2 max until exhaustion. Before and 45 min after exercise, the subjects were given either a placebo (Con), sucrose (81 +/- 18 g) (Su), caffeine (384 +/- 13 mg) (Caf), or sucrose (72 +/- 22 g) plus caffeine (396 +/- 29 mg) (Su + Caf) solution. The duration of the exercise was significantly longer in Su, Caf, and Su + Caf than in Con. The duration in four of five subjects was longest in Su + Caf, although it was not significantly different from that in Su or Caf. Carbohydrate (CHO) utilization was highest in Su while fat utilization was highest in Caf. The energy supply from both sources was almost the same between Con and Su + Caf. The plasma glucose concentration was higher in Su than in Con. The plasma free fatty acid (FFA) level was higher in Caf than in Con. The plasma glucose and lactic acid concentrations were highest in Su + Caf while the plasma FFA level was the same as in Con. In conclusion, ingestion of sucrose, caffeine, or sucrose plus caffeine solution was equally effective in improving endurance during running carried out at an intensity of approximately 80% VO2 max.     

Quantitation of erythrocyte pentose pathway flux with [2-13C]glucose and 1H NMR analysis of the lactate methyl signal.

A simple and sensitive NMR method for quantifying excess (13)C-enrichment in positions 2 and 3 of lactate by (1)H NMR spectroscopy of the lactate methyl signal is described. The measurement requires neither signal calibrations nor the addition of a standard and accounts for natural abundance (13)C-contributions. As a demonstration, the measurement was applied to approximately 3 micromol of lactate generated by erythrocyte preparations incubated with [2-(13)C]glucose to determine the fraction of glucose metabolized by the pentose phosphate pathway (PP). PP fluxes were estimated from the ratio of excess (13)C-enrichment in lactate carbon 3 relative to carbon 2 in accordance with established metabolic models. Under baseline conditions, PP flux accounted for 7 +/- 2% of glucose consumption while in the presence of methylene blue, a classical activator of PP activity, its contribution increased to 27 +/- 10% of total glucose consumption (P < 0.01).     

Effects of acute and chronic metoprolol administration during submaximal and maximal exercise

The effects of different dosages of the beta 1-adrenoceptor blocker metoprolol and of acute and chronic administration of this beta-blocker during physical exercise were compared in healthy normotensive subjects. Placebo, 0.15 mg/kg, and 0.30 mg/kg metoprolol were administered intravenously 10 min before a progressive bicycle ergometer test up to exhaustion. Thereafter, subjects were treated for 4 weeks with placebo or slow-release metoprolol (1 X 200 mg/day). At the end of each 4th week of treatment, a maximal exercise test was performed. Heart rate, ventilation, oxygen consumption, and plasma concentrations of free fatty acids, glucose, and lactate were determined at rest and during exercise. After the low (0.15 mg/kg) i.v. dose, the heart rate during maximal exercise was reduced from 189 +/- 2 to 155 +/- 2 bts/min (P less than 0.001). This reduction was significantly smaller than that after the high (0.30 mg/kg) i.v. dose (177 +/- 3 to 137 +/- 4 bts/min, P less than 0.001) and during chronic treatment (176 +/- 3 to 132 +/- 2 bts/min, P less than 0.001). The difference between the high i.v. dose and chronic treatment was not significant. After the low i.v. dose, the heart rate was the only variable affected. After the high i.v. dose, the heart rate, exercise time, maximal oxygen uptake, and plasma glucose and free fatty acid concentration during maximal exercise were reduced, and maximal lactate concentration tended to be lower. During submaximal exercise, no significant differences between placebo or beta-blocker administration were found, except for heart rate, which was reduced after beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)     

In Vivo Selective Measurement of {1−13C}-Glucose Metabolism in Tumors by Heteronuclear Cross Polarization

Selective detection of {1?¹³C}-glucose and its glycolytic product, {3?¹³C}-lactate, was achieved by selective ¹³C NMR spectroscopy with ¹H cross polarization. The total sensitivity of conventional broadband experiments was retained, and peak intensities were at least equivalent to those obtained with the inverse detection technique (i.e., ¹H{¹³C}) for single proton resonances. A key advantage of the method is that it maintains the specific absorption rate (SAR) within FDA limits of 5 W/kg by reducing power deposition during decoupling. In this study we have monitored the kinetics of metabolism of ¹³C-labeled glucose to lactate following intravenous infusion of 0.55 ml of 0.18 M labeled glucose. Physiological effects were minimized by a) maintaining total plasma glucose concentrations below 20 mM throughout the course of NMR experiment and b) by avoiding significant heating of the tumor.     

Excretion of contrast media by the immature rabbit. Comparison of Renografin and Iopamidol

The excretion of iodinated contrast media was studied in 13 immature rabbits after the intravenous injection of 2 ml/kg (approximately 600 mg I/kg) of radio-labelled Renografin-60, a high osmolality agent (1510 mOsm/kg), or Iopamidol-300, a new agent with a much lower osmolality (616 mOsm/kg). Renografin, but not Iopamidol, induced an immediate but transient 40% fall in blood pressure, a marked diuresis that was 3.4 times greater at its maximum than for Iopamidol, and a much lower urinary iodine concentration at the time of maximum diuresis (Renografin: 90.3 +/- 9.2 microgram/ml; Iopamidol: 213 +/- 32.9 microgram/ml). No difference between the two contrast media was found for plasma iodine concentration, renal clearance from the plasma, urinary iodine excretion rate or volume of distribution. In five additional rabbit pups, formal clearance studies made using a constant IV infusion of the agents and timed collections of urine and plasma showed that Iopamidol and Renografin were cleared at the same rate by the kidneys (P greater than 0.9).     

Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle

The accuracy of the measurement of total muscle glucose by in vivo ¹³C NMR spectroscopy was tested in five normal volunteers during a euglycemic [1-¹³C]glucose infusion. The NMR visible concentration calibrated using an external reference was compared with that calculated from plasma glucose concentration, assuming that glucose remained extracellular. The NMR measurement always provided higher values than the calculation from plasma glucose: 0.51 ± 0.035 (mean ± SE) versus 0.38 ± 0.005 mmol/liter of muscle on average. This systematic difference was interpreted as reflecting the presence of muscle glucose-6-phospnate, co-resonating with free glucose. Thus, glucose appeared to be virtually 100% NMR visible in human skeletal muscle.     

Acetaminophen glucuronide and plasma glucose report identical estimates of gluconeogenesis and glycogenolysis for healthy and prediabetic subjects using the deuterated water method

Plasma glucose ²H‐enrichment in positions 5 (²H5) and 2 (²H2) from deuterated water (²H₂O) provides a measure of the gluconeogenic contribution to endogenous glucose production. Urinary glucuronide analysis can circumvent blood sampling but it is not known if glucuronide and glucose enrichments are equal. Thirteen subjects with impaired fasting glucose/impaired glucose tolerance and 11 subjects with normal fasting glucose and normal glucose tolerance ingested ²H₂O to ～0.5% body water and acetaminophen. Glucose and glucuronide ²H5 and ²H2 were measured by ²H NMR spectroscopy of monoacetone glucose. For normal fasting glucose/normal glucose tolerance, ²H5 was 0.23 ± 0.02% and 0.25 ± 0.02% for glucose and glucuronide, respectively, whereas ²H2 was 0.47 ± 0.01% and 0.49 ± 0.02%, respectively. For impaired fasting glucose/impaired glucose tolerance, ²H5 was 0.22 ± 0.01% and 0.26 ± 0.02% for glucose and glucuronide, respectively, whereas ²H2 was 0.46 ± 0.01% and 0.49 ± 0.02%, respectively. The gluconeogenic contribution to endogenous glucose production measured from glucose and glucuronide were identical for both normal fasting glucose/normal glucose tolerance (48 ± 4 vs. 51 ± 3%) and impaired fasting glucose/impaired glucose tolerance (48 ± 2 vs. 53 ± 3%). Magn Reson Med 70:315–319, 2013. © 2012 Wiley Periodicals, Inc.     

Metabolic profiling of body fluids by proton NMR: self-poisoning episodes with paracetamol (acetaminophen)

1H NMR spectra of urine and plasma from subjects who had taken paracetamol (acetaminophen) at a therapeutic dose or in self-poisoning episodes (both fatal and nonfatal) are compared. They provide convenient metabolic profiles. For overdose cases, intense resonances corresponding to high levels of both drug and endogenous metabolites are observed. The ratios of glucuronide to sulfate conjugates are unusually high in urine from overdose cases. Elevated levels of the cysteinyl and N-acetyl cysteinyl conjugates reflect increased glutathione conjugation in the liver. The observed excretion of high levels of amino acids by overdose subjects is suggestive of drug-induced hepatic damage. No resonances for drug metabolites are detected in plasma samples. However, characteristic and abnormally intense resonances for the amino acids Phe, Tyr, His, Gln, Pro, Ala, Val, Lys, Met, Ser, and Thr are indicative of severe liver failure and disruption of normal deamination and transamination processes.     

Validation of 13C NMR measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples.

Recent developments in 13C nuclear magnetic resonance (NMR) spectroscopy have permitted noninvasive assessment of glycogen concentration in human skeletal muscle. Before these indirect measurements could be accepted as accurate, it was essential that validation should be carried out by comparing the widely used method of muscle biopsy and direct biochemical assay for glycogen concentration with measurement by NMR. Eight normal subjects underwent six NMR scans of gastrocnemius and three biopsies of the same muscle on the same day. The overall mean for muscle glycogen concentration was 87.4 mM by NMR and 88.3 mM by biopsy. There was a close correlation between the pairs of observations on each subject (R = 0.95; P less than 0.0001). The mean coefficient of variation for NMR measurement was 4.3 +/- 2.1% and that for biopsy was 9.3 +/- 5.9%. The performance of the muscle biopsies was accompanied by a small but significant rise in plasma-free fatty acids (529 +/- 157 to 667 +/- 250; P less than 0.01), epinephrine (17 +/- 6 to 25 +/- 8 pg/ml; P less than 0.02), and norepinephrine (318 +/- 119 to 400 +/- 140 pg/ml; P less than 0.02) but no change in plasma glucose, plasma insulin, nor muscle glycogen concentration assessed by NMR. The study demonstrates that in vivo 13C NMR measurement of human muscle glycogen can be regarded as accurate, and the technique is associated with a higher precision that biopsy with direct biochemical assessment.     

On the choice of fluid for the hydration of middle-aged marathon runners.

Nine subjects (five well-trained post-coronary patients and four other middle-aged joggers) paticipated in a 42 km "Marathon" race. The course was covered in an average of 212 minutes under pleasantly warm conditions (Maximum 21.7 degree C, 69% relative humidity). Subjects were given initial hyperhydration and repeated subsequent doses of water, "Erg" (Na+ 19mE/l K+ 10.7mE/l, glucose 5.3g/100 ml) or a "Special Solution" (during the race Na+ 21mE/1 glucose 4.1g/100 ml; after the race Na+ 20 mE/l, K+ 4.7mE/l., glucose 4.1 g/100 ml). Weight loss averaged 2.2 kg and sweat production 3.3l taking account of water liberated from the hydration of glycogen and the oxidation of food stuffs, it was estimated that most subjects suffered relatively little dehydration over the race (0.4--0.8l). This was confirmed by a sustained urine production of greater than 100ml/hr. Nevertheless, rectal temperatures showed substantial elevation over the race (final readings 38.3 - 40.2 degree C). In terms of fluid balance and stability of plasma mineral composition, the runners drinking water performed slightly better than those receiving the other two solutions. Nevertheless, there may be merit in giving potassium solutions during recovery from vigorous effort.     

Comparison of [3,4‐13C2]glucose to [6,6‐2H2]glucose as a tracer for glucose turnover by nuclear magnetic resonance

A recently introduced tracer, [3,4‐¹³C₂]glucose, was compared to the widely used tracer, [6,6‐²H₂]glucose, for measurement of whole‐body glucose turnover. The rate of glucose production (GP) was measured in rats after primed infusions of [3,4‐¹³C₂]glucose, [6,6‐²H₂]glucose, or both tracers simultaneously followed by a constant infusion of tracer(s) over 90 min. Blood glucose was purified and converted into monoacetone glucose for analysis by ¹³C NMR (for [3,4‐¹³C₂]glucose) or ¹H and ²H NMR (for [6,6‐²H₂]glucose). The values of GP measured during infusion of each single tracer were not significantly different. In rats infused with both tracers simultaneously, GP was identical as reported by each tracer, 42 ± 4 μmol/kg/min. Since ²H and ¹³C enrichment in glucose is typically much less than 2% for in vivo studies, [3,4‐¹³C₂]glucose does not interfere with measurements of ¹³C or ²H enrichment patterns and therefore is valuable when multiple metabolic pathways are being evaluated simultaneously. Magn Reson Med 53:1479–1483, 2005. © 2005 Wiley‐Liss, Inc.     

Exercise-induced changes in insulin action and glycogen metabolism in elderly adults

PURPOSE: Although data suggest that physical activity is associated with decreased insulin resistance, recommendations for exercise training are not specific for age or level of obesity. Therefore, we examined the influence of moderate-intensity (50% of VO2max) exercise training (MI) versus high-intensity (75% of VO2max) exercise training (HI) on insulin-stimulated glucose disposal (ISGD) in elderly individuals. METHODS: Following medical examinations, 21 overweight (body mass index = 29 +/- 1 kg x m(-2)) elderly (74 +/- 1 yr) subjects were randomized to 1) HI, 2) MI, or a 3) nonexercising control group. Subjects enrolled in HI or MI completed a 12-wk exercise training regimen designed to expend 1000 kcal x wk. ISGD was assessed using a hyperinsulinemic, euglycemic clamp pre- and postintervention. ISGD was corrected for hepatic glucose production (glucose Ra) using a constant rate infusion of [6,6-H2]glucose and determined during the last 30 min of the clamp by subtracting glucose Ra from the exogenous glucose infusion rate. Nonoxidative glucose disposal was calculated using indirect calorimetry. Body composition testing was completed using dual energy x-ray absorptiometry. RESULTS: ISGD increased by approximately 20% with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)). However, ISGD did not change (Delta of -0.4 +/- 0.1 mg x kg(-1) FFM.min(-1)) with MI and was not different (Delta of -0.2 +/- 0.1 mg x kg(-1) FFM.min(-1)) in the control group. Nonoxidative glucose disposal increased with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)), but there was no change in nonoxidative glucose disposal with MI or in the control group. No change in body weight or percentage of body fat was observed in any group. CONCLUSION: In weight-stable subjects, MI resulted in no change in ISGD, and the improvement in ISGD with HI was completely reliant on improvements in nonoxidative glucose disposal.     

Lactate isotopomer analysis by 1H NMR spectroscopy: consideration of long-range nuclear spin-spin interactions.

Lactate is a key metabolite and its rates of cellular uptake and release, its production rates from glucose and glycogen, and its interconversion rate with pyruvate are important determinants of cellular energy production. If lactate precursors such as pyruvate and glucose are labeled appropriately with (13)C, (1)H NMR spectroscopy provides a means of quantifying lactate production from each source and allows measurement of all these rates within a single experiment. However, due to the multiplicities of the resonance lines (from nuclear spin-spin couplings) in lactate (13)C isotopomers, the (1)H NMR spectra were found to be more complex than expected, requiring determination of all spin-spin interactions in this anion. All such values were determined for lactate and its precursor pyruvate. The method was then applied to simultaneously measure the rates of exogenous lactate uptake and rates of release of glucose-, glycogen-, and pyruvate-derived lactate in the isolated perfused rat heart.     

The effects of glucose, fructose, and sucrose ingestion during exercise

The purpose of this study was to compare the physiological, sensory, and exercise performance responses to ingestion of 6% glucose, 6% fructose, and 6% sucrose solutions during cycling exercise. Twelve subjects completed three sessions consisting of 115 min of intermittent cycle ergometer exercise at 65-80% of VO2max followed by a timed performance bout requiring the completion of 600 pedal revolutions. During each of five 4-min rest periods, subjects consumed 3 ml.kg LBM-1 of one of the beverages. Beverages were presented in counterbalanced, double-blind fashion. Heart rate, VO2, plasma urate, plasma lactate, respiratory exchange ratio, and carbohydrate combustion rates changed similarly among beverage treatment. However, fructose was associated with lower plasma glucose and serum insulin, a larger loss of plasma volume, greater gastrointestinal distress and relative perceived exertion ratings, and higher plasma or serum concentrations of free fatty acids, fructose, and cortisol values than sucrose or glucose (P less than 0.05). Compared to sucrose and glucose, fructose feeding also resulted in lower lactate and HR values during the performance bout (P less than 0.05). Mean +/- SE cycling performance times were faster with sucrose and glucose than with fructose: 419.4 +/- 21.0 s, 423.9 +/- 21.2 s, and 488.3 +/- 21.1 s, respectively (P less than 0.05). Relative to 6% solutions of sucrose and glucose, ingestion of a 6% fructose beverage is associated with gastrointestinal distress, compromised physiological response, and reduced exercise capacity.     

1-13C]glucose MRS in chronic hepatic encephalopathy in man.

[1-13C]-labeled glucose was infused intravenously in a single dose of 0.2 g/kg body weight over 15 min in six patients with chronic hepatic encephalopathy, and three controls. Serial 13C MR spectra of the brain were acquired. Patients exhibited the following characteristics relative to normal controls: 1) Cerebral glutamine concentration was increased (12.6 +/- 3.8 vs. 6.5 +/- 1.9 mmol/kg, P < 0.006) and glutamate was reduced (8.2 +/- 1.0 vs. 9.9 +/- 0.6 mmol/kg, P < 0.02). 2) 13C incorporation into glutamate C4 and C2 positions was reduced in patients (80 min after start of infusion C4: 0.43 +/- 0.09 vs. 0.84 +/- 0.15 mmol/kg, P < 0.001; C2: 0.20 +/- 0.03 vs. 0.45 +/- 0.07 mmol/kg, P < 0.0001). 3) 13C incorporation into bicarbonate was delayed (90 +/- 21 vs. 40 +/- 10 min, P < 0.003), and the time interval between detection of glutamate C4 and C2 labeling was longer in patients (22 +/- 8 vs. 12 +/- 3 min, P < 0.03). 4) Glutamate C2 turnover time was reduced in chronic hepatic encephalopathy (17.1 +/- 6.8 vs. 49.6 +/- 8.7 min, P < 0.0002). 5) 13C accumulation into glutamine C2 relative to its substrate glutamate C2 increased progressively with the severity of clinical symptoms (r = 0.96, P < 0.01). These data indicate disturbed neurotransmitter glutamate/glutamine cycling and reduced glucose oxidation in chronic hepatic encephalopathy. [1-13C] glucose MRS provides novel insights into disease progression and the pathophysiology of chronic hepatic encephalopathy.