Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men

To assess the effects of endurance training on plasma glucose kinetics during moderate-intensity exercise in men, seven men were studied before and after 12 wk of strenuous exercise training (3 days/wk running, 3 days/wk cycling). After priming of the glucose and bicarbonate pools, [U-13C] glucose was infused continuously during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2) to determine glucose turnover and oxidation. Training increased cycle ergometer peak VO2 by 23% and decreased the respiratory exchange ratio during the final 30 min of exercise from 0.89 +/- 0.01 to 0.85 +/- 0.01 (SE) (P less than 0.001). Plasma glucose turnover during exercise decreased from 44.6 +/- 3.5 mumol.kg fat-free mass (FFM)-1.min-1 before training to 31.5 +/- 4.3 after training (P less than 0.001), whereas plasma glucose clearance (i.e., rate of disappearance/plasma glucose concentration) fell from 9.5 +/- 0.6 to 6.4 +/- 0.8 ml.kg FFM-1.min-1 (P less than 0.001). Oxidation of plasma-derived glucose, which accounted for approximately 90% of plasma glucose disappearance in both the untrained and trained states, decreased from 41.1 +/- 3.4 mumol.kg FFM-1.min-1 before training to 27.7 +/- 4.8 after training (P less than 0.001). This decrease could account for roughly one-half of the total reduction in the amount of carbohydrate utilized during the final 30 min of exercise in the trained compared with the untrained state.     

Ethanol administration fails to produce hypoglycemia in fasted chickens (Gallus domesticus)

Chickens weighing approx. 1500 g were fasted 64 hr and then continuously infused with [6-3H]glucose to determine effects of ethanol on plasma glucose concentrations and on rates of glucose turnover. Ethanol infusions (222 or 444 mumol/min X kg-1 body weight) did not cause hypoglycemia although the high dose infusion slightly decreased the rate of glucose turnover. Metabolite ratios measured in livers of chickens infused with the high dose of ethanol indicated that the hepatic cytosolic redox state was relatively unchanged. Chickens have an unusual resistance to ethanol-induced hypoglycemia.     

Effect of oleic acid on the production of ethanol and fructose from glucose/fructose mixtures in an immobilized cell reactor

Saccharomyces cerevisiae ATCC 39859 was immobilized onto small cubes of wood to produce ethanol and very enriched fructose syrup from glucose/fructose mixtures through the selective fermentation of glucose. A maximum ethanol productivity of 21.9 g/l-h was attained from a feed containing 9.7% (w/v) glucose and 9.9% (w/v) fructose. An ethanol concentration, glucose conversion and fructose yield of 29.6 g/l, 62% and 99% were obtained, respectively. This resulted in a final fructose/glucose ratio of 2.7. At lower ethanol productivity levels the fructose/glucose ratio increases, as does the ethanol concentration in the effluent. The addition of 30 mg/l oleic acid to the medium increased the ethanol productivity and its concentration by 13% at a dilution rate of 0.74 h^?1.     

Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans

Oral fructose empties from the stomach more rapidly and may suppress food intake more than oral glucose. The purpose of the study was to evaluate the effects of intraduodenal infusions of fructose and glucose on antropyloric motility and appetite. Ten healthy volunteers were given intraduodenal infusions of 25% fructose, 25% glucose, or 0.9% saline (2 ml/min for 90 min). Antropyloric pressures, blood glucose, and plasma insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) were measured concurrently; a buffet meal was offered at the end of the infusion. Intraduodenal fructose and glucose suppressed antral waves (P < 0. 0005 for both), stimulated isolated pyloric pressure waves (P < 0.05 for both), and increased basal pyloric pressure (P = 0.10 and P < 0. 05, respectively) compared with saline, without any significant difference between them. Intraduodenal glucose increased blood glucose (P < 0.0005), as well as plasma insulin (P < 0.0005) and GIP (P < 0.005) more than intraduodenal fructose, whereas there was no difference in the GLP-1 response. Intraduodenal fructose suppressed food intake compared with saline (P < 0.05) and glucose (P = 0.07). We conclude that, when infused intraduodenally at 2 kcal/min for 90 min 1) fructose and glucose have comparable effects on antropyloric pressures, 2) fructose tends to suppress food intake more than glucose, despite similar GLP-1 and less GIP release, and 3) GIP, rather than GLP-1, probably accounts for the greater insulin response to glucose than fructose.     

Effects of fructose on hepatic glucose metabolism in humans

Hepatic and extrahepatic insulin sensitivity was assessed in six healthy humans from the insulin infusion required to maintain an 8 mmol/l glucose concentration during hyperglycemic pancreatic clamp with or without infusion of 16.7 micromol. kg(-1). min(-1) fructose. Glucose rate of disappearance (GR(d)), net endogenous glucose production (NEGP), total glucose output (TGO), and glucose cycling (GC) were measured with [6,6-(2)H(2)]- and [2-(2)H(1)]glucose. Hepatic glycogen synthesis was estimated from uridine diphosphoglucose (UDPG) kinetics as assessed with [1-(13)C]galactose and acetaminophen. Fructose infusion increased insulin requirements 2.3-fold to maintain blood glucose. Fructose infusion doubled UDPG turnover, but there was no effect on TGO, GC, NEGP, or GR(d) under hyperglycemic pancreatic clamp protocol conditions. When insulin concentrations were matched during a second hyperglycemic pancreatic clamp protocol, fructose administration was associated with an 11.1 micromol. kg(-1). min(-1) increase in TGO, a 7.8 micromol. kg(-1). min(-1) increase in NEGP, a 2.2 micromol. kg(-1). min(-1) increase in GC, and a 7.2 micromol. kg(-1). min(-1) decrease in GR(d) (P < 0. 05). These results indicate that fructose infusion induces hepatic and extrahepatic insulin resistance in humans.     

Glycogen depletion during prolonged exercise: influence of glucose, fructose, or placebo

We examined the influence of various carbohydrates of fuel homeostasis and glycogen utilization during prolonged exercise. Seventy-five grams of glucose, fructose, or placebo were given orally to eight healthy males 45 min before ergometer exercise performed for 2 h at 55% of maximal aerobic power (VO2max). After glucose ingestion, the rises in plasma glucose (P less than 0.01) and insulin (P less than 0.001) were 2.4- and 5.8-fold greater than when fructose was consumed. After 30 min of exercise following glucose ingestion, the plasma glucose concentration had declined to a nadir of 3.9 +/- 0.3 mmol/l, and plasma insulin had returned to basal levels. The fall in plasma glucose was closely related to the preexercise glucose (r = 0.98, P less than 0.001) and insulin (r = 0.66, P less than 0.05) levels. The rate of endogenous glucose production and utilization rose similarly by 2.8-fold during exercise in fructose group and were 10-15% higher than in placebo group (P less than 0.05). Serum free fatty acid levels were 1.5- to 2-fold higher (P less than 0.01) after placebo than carbohydrate ingestion. Muscle glycogen concentration in the quadriceps femoris fell in all three groups by 60-65% (P less than 0.001) during exercise. These data indicate that fructose ingestion, though causing smaller perturbations in plasma glucose, insulin, and gastrointestinal polypeptide (GIP) levels than glucose ingestion, was no more effective than glucose or placebo in sparing glycogen during a long-term exercise.     

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin for 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6-3H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 microU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. It is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.     

Effects of medium-chain triglyceride feeding or glucose infusion on glucose kinetics in the newborn rat

Hypoglycaemia which develops in starved newborn rats (0.15 +/- 0.01 mg/ml) is reversed by feeding medium-chain triglycerides (0.66 +/- 0.05 mg/ml). Despite similar glycaemia (0.71 +/- 0.07 mg/ml) starved newborns infused with glucose (10.7 mg/min/kg) show a 30% higher glucose turnover rate than medium-chain triglyceride fed animals (14.1 +/- 0.6 versus 10.6 +/- 0.3 mg/min/kg, p less than 0.01). For a comparable [6-3H]glucose turnover rate (10.5 +/- 0.3 mg/min/kg), glucose-infused (5.25 mg/min/kg) newborns have a 30% lower glycaemia (0.50 +/- 0.03 mg/ml, p less than 0.01) than medium-chain triglyceride-fed newborns. Thus, medium chain triglyceride feeding leads to a 30% decreased capacity of the tissues to utilize glucose. For a similar glucose turnover rate, medium-chain triglyceride-fed newborns have a higher blood lactate concentration than glucose-infused newborns (0.26 +/- 0.03 versus 0.15 +/- 0.02 mg/ml). However, in medium-chain triglyceride-fed newborns, the increase of blood lactate is not only due to the Cori cycle, as glucose recycling is less increased than glucose production. Thus medium-chain triglyceride increases the release of gluconeogenic precursors which are not derived from blood glucose. In presence of a glucose infusion (15.25 mg/min/kg) producing hyperglycaemia (1.35 +/- 0.05 mg/ml), endogenous glucose production is suppressed by only 37%. If 3-mercaptopicolinate, an inhibitor or gluconeogenesis, is given concomitantly, hyperglycaemia is prevented (0.72 +/- 0.08 mg/ml) and endogenous glucose production is suppressed. Glucose infusion in the hypoglycaemic newborn rat might thus lead to a precarious glucose homeostasis.     

Mechanism of the stimulatory effect of fructose on ethanol oxidation in perfused rat liver.

The stimulatory effect of fructose on ethanol oxidation was studied in livers from fasted rats perfused with Krebs-Henseleit-bicarbonate buffer in a non-recirculating system. Two series of experiments were performed: (A) ethanol was infused with stepwise increasing concentrations (0.1-20 mM) in the presence of 4 mM fructose; (B) fructose was infused with stepwise increasing concentrations (0.5-10 mM) in the presence of 2 mM ethanol. From measured metabolic rates the following parameters were calculated: energy-rich phosphates consumed for fructose metabolism which were provided from oxidative phosphorylation (delta approximately P); reducing equivalents derived from stimulated ethanol utilization which were disposed by mitochondrial oxidation (delta2H). Under the various conditions studied a linear relationship between these parameters was observed. The ratio delta approximately P/delta2H was about 2.0. It is suggested that fructose stimulates ethanol oxidation indirectly by increasing the energy consumption of the liver due to the production of glucose from fructose. Consequetnly, the rate of oxidative phosphorylation is increased and, therefore, the capacity of the respiratory chain for oxidizing reducing equivalents derived from ethanol is enhanced. The data support the more general hypothesis that the rate of ethanol oxidation depend upon the rate of hepatic energy consumption in a given metabolic state.     

L-Arginine infusion increases glucose clearance during prolonged exercise in humans

Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate exercise-induced increases in muscle glucose uptake. We examined the effect of infusing the NO precursor L-arginine (L-Arg) on glucose kinetics during exercise in humans. Nine endurance-trained males cycled for 120 min at 72+/-1% Vo(2 peak) followed immediately by a 15-min "all-out" cycling performance bout. A [6,6-(2)H]glucose tracer was infused throughout exercise, and either saline alone (Control, CON) or saline containing L-Arg HCL (L-Arg, 30 g at 0.5 g/min) was confused in a double-blind, randomized order during the last 60 min of exercise. L-Arg augmented the increases in glucose rate of appearance, glucose rate of disappearance, and glucose clearance rate (L-Arg: 16.1+/-1.8 ml.min(-1).kg(-1); CON: 11.9+/- 0.7 ml.min(-1).kg(-1) at 120 min, P<0.05) during exercise, with a net effect of reducing plasma glucose concentration during exercise. L-Arg infusion had no significant effect on plasma insulin concentration but attenuated the increase in nonesterified fatty acid and glycerol concentrations during exercise. L-Arg infusion had no effect on cycling exercise performance. In conclusion, L-Arg infusion during exercise significantly increases skeletal muscle glucose clearance in humans. Because plasma insulin concentration was unaffected by L-Arg infusion, greater NO production may have been responsible for this effect.     

Kinetic analysis for the isomerization of glucose,fructose, and mannose in subcritical aqueous ethanol

Fructose, glucose, and mannose were treated with subcritical aqueous ethanol for ethanol concentrations ranging from 0 to 80% (v/v) at 180–200 °C. The aldose–ketose isomerization was more favorable than ketose–aldose isomerization and glucose–mannose epimerization. The isomerization of the monosaccharides was promoted by the addition of ethanol. In particular, mannose was isomerized most easily to fructose in subcritical aqueous ethanol. The apparent equilibrium constants for the isomerizations of mannose to fructose, K_eq,M→F, and glucose to fructose, K_eq,G→F, were independent of ethanol concentration and increased with increasing temperature. Moreover, the K_eq,M→F value was much larger than the K_eq,G→F value. The enthalpies for the isomerization of mannose to fructose, ΔH_M→F, and glucose to fructose, ΔH_G→F, were estimated to be 18 and 24 kJ/mol, respectively, according to van’t Hoff equation. Subcritical aqueous ethanol can be used to produce fructose from glucose and mannose efficiently.     

Production of 1,3-propanediol, 2,3-butanediol and ethanol by a newly isolated Klebsiella oxytoca strain growing on biodiesel-derived glycerol based media

The production of 1,3-propanediol, 2,3-butanediol and ethanol was studied, during cultivations of strain Klebsiella oxytoca FMCC-197 on biodiesel-derived glycerol based media. Different kinds of glycerol feedstocks and experimental conditions had an important impact upon the distribution of metabolic products; production of 1,3-propanediol was positively influenced by stable pH conditions and by the absence of N₂ gas infusions throughout the fermentation. Thus, during batch bioreactor fermentations conducted at increasing glycerol concentrations, 1,3-propanediol at 41.3 g/L and yield ～47% (w/w) was achieved at initial glycerol concentration ～120 g/L. At even higher initial glycerol media (150 and 170 g/L), growth was not ceased, but 1,3-propanediol production declined. During fed-batch fermentation under optimal experimental conditions, 126 g/L of glycerol were converted into 50.1 g/L of 1,3-propanediol. In this experiment, also 25.2 g/L of ethanol (conversion yield ～20%, w/w) were formed. A batch-bioreactor culture was performed under non-sterilized conditions and the 1,3-propanediol production was almost equivalent to the sterilized process. Concerning 2,3-butanediol formation, the most detrimental parameter was the absence of N₂ sparging and as a result, no 2,3-butanediol was produced. The presence of glucose as co-substrate seriously enhanced 2,3-butanediol production; when commercial glucose was employed as sole substrate, 32.1 g/L of 2,3-butanediol were formed.     

Continuous production of fructose syrup and ethanol from hydrolysed Jerusalem artichoke juice

Summary The results from this study showed that Jerusalem artichoke juice can be used for the production of very enriched fructose syrup by selective conversion of glucose to ethanol in a continuous process using immobilized cells ofSaccharomyces cerevisiae ATCC 36859. The product contained up to 99% of the total carbohydrates as fructose compared to 76% in the feed. Using Jerusalem artichoke juice supplemented with some glucose a product was obtained with 7.5% w/v ethanol which made ethanol recovery economically favourable. It was found that some fructose was consumed in these continuous processes; the glucose/fructose conversion rate ratio was regulated by the glucose concentration in the product stream.     

Effect of hyperammonaemia on blood glucose and plasma insulin levels in sheep.

The effects of continuous intravenous infusions (6 h) of ammonium chloride (5.6; 11.2; and 16.8 mumol.kg-1.min) on plasma glucose and immunoreactive insulin (I.R.I.) levels were studied in three adult sheep. Infusions of 5.6 and 11.2 mumol.kg-1.min elevated ammonia levels in circulating blood from 100 to 150 and 300 microgram.100 ml-1, respectively, but showed no appreciable effect on plasma glucose and I.R.I. concentrations. Infusion of 16.8 mumol.kg-1.min-1 resulted in a blood ammonia concentration of about 400 microgram.100 ml-1 after six hours of infusion. Blood ammonia returned to normal 1 to 2 hours after the end of infusion. Plasma glucose concentration tended to increase slightly from 65 to 75 mg . 100 ml-1 when 16.8 mumol of NH4Cl were infused kg-1.min-1 and remained at the elevated level at least for two additional hours when ammonia infusions were stopped. Plasma I.R.I. tended to decrease from 48 to 38 microunits . ml-1 during the time of the NH4Cl infusion and increased continually to 82 microunits . ml-1 when NH4Cl infusions were stopped. It is concluded from the time courses of plasma glucose and plasma I.R.I. that the effect of ammonia infusion of these parameters cannot entirely be explained by a regulatory release of adrenaline.     

Kinetics of the selective fermentation of glucose from glucose/fructose mixtures using Saccharomyces cerevisiae ATCC 36859

The kinetics of batch fermentation during the growth of S. cerevisiae ATCC 36859 was studied in various glucose/fructose mixtures. It was found that the growth is inhibited equally by glucose and fructose even though fructose is not consumed to any large extent by the yeast under the conditions tested here. The inhibition of growth by the substrate and ethanol is represented by linear equations. These equations were combined with the MONOD expression in order to formulate equations for the biomass growth, glucose and fructose consumption and ethanol production. Parameter estimates were obtained by fitting these equations to batch fermentation data and so developing models which indicate that the growth is completely inhibited when 62 g/l ethanol is produced by the yeast, while glucose consumption and ethanol production continue up to an ethanol concentration of 152 g/l. Products containing a high concentration of fructose are best produced by using a high initial biomass concentration.     

Fed-batch production of concentrated fructose syrup and ethanol using Saccharomyces cerevisiae ATCC 36859

A fed-batch process is used for the production of concentrated pure fructose syrup and ethanol from various glucose/fructose mixtures by S. cerevisiae ATCC 36859. Applying this technique, glucose-free fructose syrups with over 250 g/l of this sugar were obtained using High Fructose Corn Syrup and hydrolyzed Jerusalem artichoke juice. By encouraging ethanol evaporation from the reactor and condensing it, a separate ethanol product with a concentration of up to 350 g/l was also produced. The rates of glucose consumption and ethanol production were higher than in classical batch ethanol fermentation processes.     

The effect of ethanol or sorbitol on glucose production from pyruvate in isolated hepatocytes from 48-hour fasted guinea-pigs

Hepatocytes isolated from 48-hour, fasted guinea-pigs were incubated with glucose precursors to compare relative rates of glucose production. Glucose production from lactate and pyruvate was similar (2.61 vs 3.18 mumol/hr per 100 mg wet weight). Glucose production from fructose was greater than that from sorbitol (4.68 vs 1.63 mumol/hr per 100 mg wet weight). When ethanol was added to pyruvate-containing buffer, the flux of pyruvate to glucose and lactate was synergistically enhanced (5.28 vs 3.76 and 7.51 vs 2.88 mumol/hr per 100 mg wet weight, respectively). When sorbitol was added to buffer containing pyruvate, glucose and lactate production were even greater than that seen with ethanol (8.32 vs 5.38 and 15.99 vs 7.51 mumol/hr per 100 mg wet weight, respectively).     

Oxidation of a glucose polymer during exercise: comparison with glucose and fructose

The purpose of this study was to compare the oxidation of 13C-labeled glucose, fructose, and glucose polymer ingested (1.33 g.kg-1 in 19 ml.kg-1 water) during cycle exercise (120 min, 53 +/- 2% maximal O2 uptake) in six healthy male subjects. Oxidation of exogenous glucose and glucose polymer (72 +/- 15 and 65 +/- 18%, respectively, of the 98.9 +/- 4.7 g ingested) was similar and significantly greater than exogenous fructose oxidation (54 +/- 13%). A transient rise in plasma glucose concentration was observed with glucose ingestion only. However, plasma insulin levels were similar with glucose and glucose polymer ingestions and significantly higher than with water or fructose ingestion. Plasma free fatty acid and glycerol responses to exercise were blunted with carbohydrate ingestion. However, fat utilization was not significantly different with water (82 +/- 14 g), glucose (60 +/- 3 g), fructose (59 +/- 11 g), or glucose polymer ingestion (60 +/- 8 g). Endogenous carbohydrate utilization was significantly lower with glucose (184 +/- 22 g), glucose polymer (187 +/- 31 g), and fructose (211 +/- 18 g) than with water (239 +/- 30 g) ingestion. Plasma volume slightly increased with water ingestion (7.4 +/- 4.5%), but the decrease was similar with glucose (-7.6 +/- 5.1%) and glucose polymer (-8.2 +/- 4.6%), suggesting that the rate of water delivery to plasma was similar with the two carbohydrates.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of fructose and its metabolites on ethanol metabolism in vitro

1. Fructose caused an increase in the rate of ethanol oxidation by rat-liver slices, and d-glyceraldehyde was found to have a similar effect. 2. Addition of glycerol lowered the rate of ethanol oxidation if the incubation medium contained fructose and ethanol, but no such effect was found if it contained glucose and ethanol. 3. The formation of glycerol by the slices during incubation and the concentration of alpha-glycerophosphate in the slices were highest in medium containing fructose and ethanol. 4. In experiments without ethanol in the incubation medium, fructose strongly increased the pyruvate concentration, which resulted in a decrease of the lactate/pyruvate concentration ratio. Addition of ethanol to the medium resulted in a marked decrease in pyruvate concentration. 5. Oxygen consumption is greater in slices incubated in medium containing fructose and ethanol than in slices incubated in medium containing glucose and ethanol.     

Ethanol stimulates glycogenolysis in livers from fed rats.

To determine the reason for the lack of a hypoglycemic effect of ethanol in the fed state, the effect of ethanol on glucose turnover, liver glycogenolysis, and glucose metabolites was determined. Chronically catheterized awake and freely moving fed rats received either ethanol (blood ethanol, 37 +/- 10 mmol/liter, n = 11) or saline (n = 13) intravenously for 4 hr. Glucose turnover was determined using a primed continuous infusion of [3-3H]glucose. The liver was freeze clamped at 4 hr for glycogen and metabolite measurements. Plasma glucose (5.8 +/- 0.3 mmol/liter vs 6.3 +/- 0.2 mmol/liter at 4 hr, ethanol versus saline) and the rate of glucose turnover (61 +/- 9 vs 58 +/- 8 moles/kg.min) were similar during the ethanol and saline infusions. Plasma lactate was significantly higher in the ethanol (1.32 +/- 0.05 mmol/liter) than in the saline (0.86 +/- 0.06 mmol/liter, P less than 0.001) study. Concentrations of gluconeogenic intermediates in the liver (glucose 6-phosphate, fructose 6-phosphate, glucose 1-phosphate, and pyruvate) were all significantly and -30% lower in ethanol-infused than in saline-infused rats. The liver citrate content was similar in ethanol-infused than in saline-infused rats. The liver citrate content was similar in ethanol (0.38 +/- 0.03 mmol/liter) and saline (0.37 +/- 0.04 mmol/liter) studies. Liver glycogen was 75% lower in the ethanol-infused (61 +/- 9 mmol/kg dry wt) than the saline (242 +/- 27 mmol/kg dry wt, P less than 0.001)-infused rats. These data demonstrate that in fed rats given ethanol, glucose turnover is maintained constant by accelerated glycogenolysis. Thus, inhibition of gluconeogenesis by ethanol does not lower hepatic glucose production unless compensatory glycogenolysis can be prevented.