Muscle Glucose Concentrations Research Articles

Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test

Aims/hypothesisExercise has a profound effect on insulin sensitivity in skeletal muscle. The euglycaemic–hyperinsulinaemic clamp (EHC) is the gold standard for assessment of insulin sensitivity but it does not reflect the hyperglycaemia that occurs after eating a meal. In previous EHC investigations, it has been shown that the interstitial glucose concentration in muscle is decreased to a larger extent in previously exercised muscle than in rested muscle. This suggests that previously exercised muscle may increase its glucose uptake more than rested muscle if glucose supply is increased by hyperglycaemia. Therefore, we hypothesised that the exercise-induced increase in muscle insulin sensitivity would appear greater after eating a meal than previously observed with the EHC.MethodsTen recreationally active men performed dynamic one-legged knee extensor exercise for 1 h. Following this, both femoral veins and one femoral artery were cannulated. Subsequently, 4 h after exercise, a solid meal followed by two liquid meals were ingested over 1 h and glucose uptake in the two legs was measured for 3 h. Muscle biopsies from both legs were obtained before the meal test and 90 min after the meal test was initiated. Data obtained in previous studies using the EHC (n=106 participants from 13 EHC studies) were used for comparison with the meal-test data obtained in this study.ResultsPlasma glucose and insulin peaked 45 min after initiation of the meal test. Following the meal test, leg glucose uptake and glucose clearance increased twice as much in the exercised leg than in the rested leg; this difference is twice as big as that observed in previous investigations using EHCs. Glucose uptake in the rested leg plateaued after 15 min, alongside elevated muscle glucose 6-phosphate levels, suggestive of compromised muscle glucose metabolism. In contrast, glucose uptake in the exercised leg plateaued 45 min after initiation of the meal test and there were no signs of compromised glucose metabolism. Phosphorylation of the TBC1 domain family member 4 (TBC1D4; p-TBC1D4Ser704) and glycogen synthase activity were greater in the exercised leg compared with the rested leg. Muscle interstitial glucose concentration increased with ingestion of meals, although it was 16% lower in the exercised leg than in the rested leg.Conclusions/interpretationHyperglycaemia after meal ingestion results in larger differences in muscle glucose uptake between rested and exercised muscle than previously observed during EHCs. These findings indicate that the ability of exercise to increase insulin-stimulated muscle glucose uptake is even greater when evaluated with a meal test than has previously been shown with EHCs.Graphical

Investigating sensor location on the effectiveness of continuous glucose monitoring during exercise in a non-diabetic population

ABSTRACT The purpose of this investigation was to evaluate whether continuous glucose monitoring (CGM) sensors worn on the active muscle may provide enhanced insight into glucose control in non-diabetic participants during cycling exercise compared to traditional sensor placement on the arm. Data from 9 healthy participants (F:3) was recorded using CGM sensors on the arm (triceps brachii) and leg (vastus medialis) following 100 g glucose ingestion during 30 min experimental visits of: resting control, graded cycling, electrically stimulated quadriceps contractions, and passive whole-body heating. Finger capillary glucose was used to assess sensor accuracy. Under control conditions, the traditional arm sensor better reflected capillary glucose, with a mean absolute relative difference (MARD) of 12.4 ± 9.3% versus 18.3 ± 11.4% in the leg (P = 0.02). For the intended use during exercise, the sensor-site difference was attenuated, with similar MARDs during cycling (arm:15.5 ± 12% versus leg:16.7 ± 10.8%, P = 0.96) and quadriceps stimulation (arm:15.5 ± 14.8% versus leg:13.9 ± 9.5%, P = 0.9). At rest, glucose at the leg was consistently lower than the arm (P = 0.01); whereas, during graded cycling, the leg-glucose was lower only after maximal intensity exercise (P = 0.02). There was no difference between sensors during quadriceps stimulation (P = 0.8). Passive heating caused leg-skin temperature to increase by 3.1 ± 1.8°C versus 1.1 ± 0.72°C at the arm (P = 0.002), elevating MARD in the leg (23.5 ± 16.2%) and lowering glucose in the leg (P < 0.001). At rest, traditional placement of CGM sensors on the arm may best reflect blood glucose; however, during cycling, placement on the leg may offer greater insight to working muscle glucose concentrations, and this is likely due to greater blood-flow rather than muscle contractions. Highlights Wearing a continuous glucose monitoring (CGM) sensor on the arm may better reflect capillary glucose concentrations compared to wearing a sensor on the inner thigh at rest. With passive or active leg-muscle contractions, site-specific differences compared to capillary samples are attenuated; therefore, wearing a CGM sensor on the active-muscle during exercise may provide greater information to non-diabetic athletes regarding glucose flux at the active muscle. Discrepancies in CGM sensors worn at different sites likely primarily reflects differences in blood flow, as passive skin heating caused the largest magnitude difference between arm and leg sensor readings compared to the other experimental conditions (control, electric muscle stimulation, and cycling exercise).

Carbohydrate tolerance in Amazon tambaqui (Colossoma macropomum) revealed by NMR-metabolomics - Are glucose and fructose different sugars for fruit-eating fish?

In the present study, two approaches were followed to evaluate the metabolic responses of tambaqui (Colossoma macropomum), a frugivorous species, to intraperitoneal (IP) administration of glucose (GLU) and fructose (FRU) in fed (FED) and 10-day fasted (FAST) fish. Glucose and fructose tolerance tests were performed to assess the carbohydrate utilization and complementary NMR-metabolomics analyses were done to elucidate the impacts of sugar mobilization on the metabolic profile of plasma, liver and muscle. Blood was sampled from FED groups at 0, 3, 6 and 24 h; and at 0 and 24 h from FAST groups. Significant differences were observed in the hyperglycaemic peak between sugars at 3 h (GLU - 13.7 ± 2.0 mM vs. FRU - 8.7 ± 1.1 mM; saline 6.3 ± 0.6 mM) and on the return to normoglycaemia (GLU - 8.5 ± 2.2 mM vs. FRU - 5.2 ± 0.9 mM; saline 4.9 ± 0.6 mM) 6 h after IP on the FRU fish. The NMR-metabolomics approach allowed to conclude that tambaqui seems to be more responsive to the feeding regime (FED vs. FAST) than to the injected sugar (FRU vs. GLU). From the studied tissues, plasma showed no significant variations between feeding regimes at 24 h after IP, while muscle and liver revealed some variations on the final metabolome profile between FED and FAST groups. The metabolome variations between feeding regimes are indicative of changes on the amino acid utilization. Fish from FAST group seem to utilize amino acids as energy source rather than for protein synthesis and muscle growth. Variations on glucose concentration in muscle can also indicate different utilization of the sugars depending on the feeding regime.

Insulin-induced membrane permeability to glucose in human muscles at rest and following exercise.

Increased insulin action is an important component of the health benefits of exercise, but its regulation is complex and not fully elucidated. Previous studies of insulin-stimulated GLUT4 translocation to the skeletal muscle membrane found insufficient increases to explain the increases in glucose uptake. By determination of leg glucose uptake and interstitial muscle glucose concentration, insulin-induced muscle membrane permeability to glucose was calculated 4h after one-legged knee-extensor exercise during a submaximal euglycaemic-hyperinsulinaemic clamp. It was found that during submaximal insulin stimulation, muscle membrane permeability to glucose in humans increases twice as much in previously exercised vs. rested muscle and outstrips the supply of glucose, which then becomes limiting for glucose uptake. This methodology can now be employed to determine muscle membrane permeability to glucose in people with diabetes, who have reduced insulin action, and in principle can also be used to determine membrane permeability to other substrates or metabolites. Increased insulin action is an important component of the health benefits of exercise, but the regulation of insulin action in vivo is complex and not fully elucidated. Previously determined increases in skeletal muscle insulin-stimulated GLUT4 translocation are inconsistent and mostly cannot explain the increases in insulin action in humans. Here we used leg glucose uptake (LGU) and interstitial muscle glucose concentration to calculate insulin-induced muscle membrane permeability to glucose, a variable not previously possible to quantify in humans. Muscle membrane permeability to glucose, measured 4h after one-legged knee-extensor exercise, increased ∼17-fold during a submaximal euglycaemic-hyperinsulinaemic clamp in rested muscle (R) and ∼36-fold in exercised muscle (EX). Femoral arterial infusion of NG -monomethyl l-arginine acetate or ATP decreased and increased, respectively, leg blood flow (LBF) in both legs but did not affect membrane glucose permeability. Decreasing LBF reduced interstitial glucose concentrations to ∼2mM in the exercised but only to ∼3.5mM in non-exercised muscle and abrogated the augmented effect of insulin on LGU in the EX leg. Increasing LBF by ATP infusion increased LGU in both legs with uptake higher in the EX leg. We conclude that it is possible to measure functional muscle membrane permeability to glucose in humans and it increases twice as much in exercised vs. rested muscle during submaximal insulin stimulation. We also show that muscle perfusion is an important regulator of muscle glucose uptake when membrane permeability to glucose is high and we show that the capillary wall can be a significant barrier for glucose transport.

GW24-e3076 The effect of lipioc acid and Vitamin E on the exercise ability of rats

ObjectivesExercise fatigue is a normal physiological phenomenon in human body movement, in the training process or daily physical exercise, because the body does not adapt, or exercise intensity, exercise time,...

A Fermented Soy Permeate Improves the Skeletal Muscle Glucose Level Without Restoring the Glycogen Content in Streptozotocin-Induced Diabetic Rats

Exercise is essential into the therapeutic management of diabetic patients, but their level of exercise tolerance is lowered due to alterations of glucose metabolism. As soy isoflavones have been shown to improve glucose metabolism, this study aimed to assess the effects of a dietary supplement containing soy isoflavones and alpha-galactooligosaccharides on muscular glucose, glycogen synthase (GSase), and glycogen content in a type 1 diabetic animal model. The dietary supplement tested was a patented compound, Fermented Soy Permeate (FSP), developed by the French Company Sojasun Technologies. Forty male Wistar rats were randomly assigned to control or diabetic groups (streptozotocin, 45 mg/kg). Each group was then divided into placebo or FSP-supplemented groups. Both groups received by oral gavage, respectively, water or diluted FSP (0.1 g/day), daily for a period of 3 weeks. At the end of the protocol, glycemia was noticed after a 24-h fasting period. Glucose, total GSase, and the glycogen content were determined in the skeletal muscle (gastrocnemius). Diabetic animals showed a higher blood glucose concentration, but a lower glucose and glycogen muscle content than controls. Three weeks of FSP consumption allowed to restore the muscle glucose concentration, but failed to reduce glycemia and to normalize the glycogen content in diabetic rats. Furthermore, the glycogen content was increased in FSP-supplemented controls compared to placebo controls. Our results demonstrated that diabetic rats exhibited a depleted muscle glycogen content (-25%). FSP-supplementation normalized the muscle glucose level without restoring the glycogen content in diabetic rats. However, it succeeded to increase it in the control group (+20%).

Augmented postmortem glycolysis does not occur early postmortem in AMPKγ3-mutated porcine muscle of halothane positive pigs

The objective of this study was to determine the effects of the halothane (HAL) and Rendement Napole (RN) genes on the rate-limiting reactions of glycolysis and their relationship to pork quality development. Samples were collected from the longissimus muscle at 0, 30, 60, and 120 min and 24 h postmortem from homozygous HAL and RN pigs (NN/rn +rn +, NN/RN −RN −, nn/rn +rn +, nn/RN −RN −). Muscle pH was recorded at 0, 15, and 45 min, and 24 h postmortem. HAL mutants, compared with HAL normal, had lower ( P < 0.05) ATP concentrations at 0 and 30 min, lower ( P < 0.05) pH at 45 min, and hastened glycogen degradation and lactate accumulation in the first 120 min postmortem (HAL × time, P < 0.0001). RN mutants had greater ( P < 0.0001) glycolytic potentials than RN normal, and lower ( P < 0.05) 24 h pH compared with the normal genotype, but not the HAL mutant genotype. The HAL mutation negatively affected ( P < 0.05) L∗, b∗ and color scores whereas both HAL and RN mutations independently decreased ( P < 0.05) firmness, marbling and water holding capacity. RN mutant genotypes had higher ( P < 0.0001) phosphocreatine concentrations than other genotypes at 0 min. Compared with HAL normal, HAL mutants had elevated ( P < 0.05) muscle glucose concentrations at 30, 60, and 120 min, and 24 h. RN mutants had higher ( P < 0.05) glucose levels than RN normal after 60 min. Glucose-6-phosphate (G6P) concentrations decreased ( P < 0.05) during the first hour postmortem except in HAL/RN mutants, which had higher ( P < 0.01) G6P concentrations than all other genotypes at 30 min. From 60 min to 24 h postmortem, G6P increased ( P < 0.05) in HAL normal genotypes. Altogether, these data show that elevated muscle glycogen content does not further aggravate rapid early postmortem metabolism.

Limitations to basal and insulin-stimulated skeletal muscle glucose uptake in the high-fat-fed rat.

Rats fed a high-fat diet display blunted insulin-stimulated skeletal muscle glucose uptake. It is not clear whether this is due solely to a defect in glucose transport, or if glucose delivery and phosphorylation are also impaired. To determine this, rats were fed standard chow (control rats) or a high-fat diet (HF rats) for 4 wk. Experiments were then performed on conscious rats under basal conditions or during hyperinsulinemic euglycemic clamps. Rats received primed constant infusions of 3-O-methyl-[(3)H]glucose (3-O-MG) and [1-(14)C]mannitol. Total muscle glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-MG concentration [which distributes based on the transsarcolemmal glucose gradient (TSGG)] were used to calculate glucose concentrations at the inner and outer sarcolemmal surfaces ([G](im) and [G](om), respectively) in soleus. Total muscle glucose was also measured in two fast-twitch muscles. Muscle glucose uptake was markedly decreased in HF rats. In control rats, hyperinsulinemia resulted in a decrease in soleus TSGG compared with basal, due to increased [G](im). In HF rats during hyperinsulinemia, [G](im) also exceeded zero. Hyperinsulinemia also decreased muscle glucose in HF rats, implicating impaired glucose delivery. In conclusion, defects in extracellular and intracellular components of muscle glucose uptake are of major functional significance in this model of insulin resistance.

Intracellular skeletal muscle glucose metabolism is differentially altered by dexamethasone treatment of normoglycemic relatives of type 2 diabetic patients.

Young first-degree relatives of type 2 diabetic patients are insulin-resistant, with the insulin resistance mainly located in skeletal muscle due to decreased insulin-induced nonoxidative glucose metabolism and muscle glycogen synthase activation. We investigated whether the mechanism differs for dexamethasone (dex)-induced insulin resistance in first-degree relatives of type 2 diabetics versus healthy control subjects by quantifying intracellular glucose processing in muscle biopsies taken before and after 5 days of dex treatment (4 mg/d) in 20 normal glucose-tolerant relatives of type 2 diabetic patients and 20 matched controls (age, 29.4 +/- 1.7 v 29.4 +/- 1.6 years; body mass index, 25.1 +/- 1.0 v 25.1 +/- 0.9 kg/m2). In addition, an intravenous glucose tolerance test (IVGTT) combined with continuous indirect calorimetry was performed. Following 5 days of dex treatment, glucose tolerance deteriorated in both the relatives and the control subjects. Fasting dry-weight muscle glucose and fasting intracellular muscle glucose concentrations increased in response to dex only in the relatives (2.43 +/- 0.21 v 2.97 +/- 0.26 mmol/kg dry weight, P < .05; 0.28 +/- 0.07 v 0.45 +/- 0.08 mmol/L intracellular water, P < .05); no increases were observed in the control subjects. Fasting dry-weight muscle lactate also increased post-dex only in the relatives (7.37 +/- 0.40 v 10.77 +/- 1.22 mmol/kg dry weight, P < .001). Both basal muscle glucose and lactate concentrations from the IVGTT study correlated with the 2-hour post-dex glucose value obtained during the OGTT study in the relatives (R = .76 and R = .74, respectively, both P < .0001) but not in the control subjects. Basal intramuscular glycogen synthase activity decreased approximately 25% in both the relatives and control subjects post-dex; the decrement was significant (P < .01) only in control subjects. Indirect calorimetry during the post-dex IVGTT demonstrated increased glucose oxidation (P < .03) and reduced lipid oxidation (P < .03) in the relatives only. We postulate that the insulin resistance induced by dex in first-degree relatives of type 2 diabetic patients is associated with a preferential channeling of glucose into the glycolytic pathway (increased glucose oxidation and lactate production), probably associated with a preexisting downregulation of the glycosen synthase pathway.

A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo.

Intracellular glucose concentration in skeletal muscle of awake rats was determined under conditions of hyperglycemic (10.2 +/- 0.6 mM) hyperinsulinemia (approximately 1,200 pM) and hyperglycemic (20.8 +/- 1.5 mM) hypoinsulinemia (< 12 pM) by use of 13C nuclear magnetic resonance (NMR) spectroscopy during a prime-constant infusion of [1-13C]glucose and [1-13C]mannitol with either insulin (10 mU.kg-1.min-1) or somatostatin (1.0 microgram.kg-1.min-1). Intracellular glucose was calculated as the difference between the concentrations of total tissue glucose (calculated from the in vivo 13C NMR spectrum with mannitol as an internal concentration standard) and extracellular glucose, corrected by the ratio of intra- and extracellular water space. Extracellular concentration was corrected for an interstitial fluid-to-plasma glucose concentration gradient of 0.83 +/- 0.07, determined by open-flow microperfusion. The mean ratio of intra- to extracellular glucose space, determined from the relative NMR signal intensities and concentrations of mannitol and total creatine, was 9.2 +/- 1.1 (hyperglycemic hyperinsulinemia, n = 10), and 9.0 +/- 1.7 (hyperglycemic hypoinsulinemia, n = 7). Mean muscle intracellular glucose concentration was < 0.07 mM under hyperglycemic-hyperinsulinemic conditions (n = 10) and 0.32 +/- 0.06 mM under hyperglycemic-hypoinsulinemic conditions (n = 7). This method is noninvasive and should prove useful for resolving the question of whether glucose transport or phosphorylation is responsible for the reduced rate of muscle glycogen synthesis observed in diabetic subjects.

Sarcolemmal glucose transport and GLUT-4 translocation during exercise are diminished by endurance training.

Glucose utilization during exercise of a given submaximal power output is decreased after endurance training. The aim of the present study was to elucidate the mechanisms behind this phenomenon by utilizing the sarcolemmal giant vesicle technique. Eight healthy young untrained men endurance trained one thigh for 3 wk. They then exercised both thighs simultaneously at the same work load (77% of peak O2 uptake of the untrained thigh) for 40 min. Training increased muscle GLUT-4 protein by 70% (P < 0.05). Glucose uptake during exercise was 38% lower (P < 0.05) in the trained (T) thigh than in the untrained (UT) thigh because of both a lower (P < 0.05) glucose extraction and blood flow in T. During exercise, sarcolemmal GLUT-4 protein content and glucose transport capacity increased significantly less in T than in UT muscle, and muscle glucose concentration was lower in T compared with UT (P < 0.05) at the end of exercise. It is concluded that, despite a large increase in muscle GLUT-4 with endurance training, exercise of a given submaximal power output increases muscle glucose uptake less in T than in UT muscle. It is suggested that the mechanism behind this phenomenon is blunted exercise-induced translocation of GLUT-4 to the sarcolemma, resulting in a blunted increase in sarcolemmal glucose transport in T muscle.

Effects of food deprivation on white muscle energy reserves in rainbow trout (Oncorhynchus mykiss): the relationships with body size and temperature

The relationship between body size and the depletion of white muscle metabolites (e.g., PCr, ATP, glucose and glycogen) was examined in two sizes (30 or 700 g) of rainbow trout deprived of food for one, four or seven days at either 5 or 15 °C. Following 7 days of food deprivation at 15 °C, the levels of muscle glycogen decreased by approximately 50% in small fish relative to control values (i.e., day 1). In comparison, small fish acclimated to cold temperatures did not exhibit a significant reduction of muscle glycogen over the seven day fasting regime. In contrast to small fish, the levels of white muscle glycogen in large fish remained unchanged after food deprivation, regardless of acclimation temperature. A seven day deprivation of food also resulted in a 50% depletion of white muscle glucose concentrations in small and large fish acclimated to warm temperatures, but there were no significant changes in this variable in fish acclimated to cold temperatures. In contrast to the negative effects of food deprivation on white muscle glycogen and glucose levels, the concentrations of white muscle PCr and ATP were not greatly affected by food deprivation under any of the experimental conditions. Taken together, these results clearly show that food deprivation can have an important influence on the storage of energy metabolites for anaerobic energy production, particularly in small fish at warm temperatures. In the future, it may be very important to consider the physiological effects of short-term food deprivation when interpreting results from studies in which fish have been fasted prior to treatments such as exercise.

Protracted glucose fall in subcutaneous adipose tissue and skeletal muscle compared with blood during insulin-induced hypoglycaemia.

The absolute glucose concentrations in subcutaneous adipose tissue and skeletal muscle were determined with microdialysis in 10 normal-weight, healthy subjects during a standardized hyperinsulinaemic hypoglycaemic clamp. The concentration of tissue dialysate glucose was measured in 15-min fractions and compared with that in arterialized venous plasma. Insulin (0.15 U x kg(-1) x h[-1]) was infused i.v. to lower the plasma glucose level to 2.5 mmol/l over 30 min. This level was maintained for 30 min by using a variable glucose infusion. Thereafter, the insulin infusion was stopped and the plasma glucose level was gradually increased to baseline levels over 120 min. During a 60-min basal period, the glucose levels in muscle were 0.6 mmol/l lower than those in plasma (p = 0.002), whereas the levels in adipose tissue and plasma were similar. The glucose nadirs in muscle (1.6 +/- 0.1 mmol/l) and adipose tissue (2.0 +/- 0.1 mmol/l) were significantly lower than that in plasma (2.4 +/- 0.1 mmol/l) (p = 0.001 and 0.02, respectively), and the time-to-nadir was substantially longer in muscle (69 +/- 5 min) and adipose tissue (57 +/- 2 min) than in plasma (39 +/- 3 min) (p = 0.0004). When the insulin infusion was stopped, the increases in adipose tissue and muscle glucose concentrations were delayed by approximately 25 and 45 min, respectively, as compared to the increase in plasma glucose. Thus, it seems that glucose measurements in adipose tissue and muscle more adequately reflect overall tissue homeostasis than do measurements in blood and that clinically relevant tissue glucopenia may be overlooked by conventional blood glucose measurements.

Decreased insulin secretion in first-degree family members of NIDDM patients

Young first-degree relatives of type 2 diabetic patients are insulin-resistant, with the insulin resistance mainly located in skeletal muscle due to decreased insulin-induced nonoxidative glucose metabolism and muscle glycogen synthase activation. We investigated whether the mechanism differs for dexamethasone (dex)-induced insulin resistance in first-degree relatives of type 2 diabetics versus healthy control subjects by quantifying intracellular glucose processing in muscle biopsies taken before and after 5 days of dex treatment (4 mg/d) in 20 normal glucose-tolerant relatives of type 2 diabetic patients and 20 matched controls (age, 29.4 ± 1.7 v 29.4 ± 1.6 years; body mass index, 25.1 ± 1.0 v 25.1 ± 0.9 kg/m2). In addition, an intravenous glucose tolerance test (IVGTT) combined with continuous indirect calorimetry was performed. Following 5 days of dex treatment, glucose tolerance deteriorated in both the relatives and the control subjects. Fasting dry-weight muscle glucose and fasting intracellular muscle glucose concentrations increased in response to dex only in the relatives (2.43 ± 0.21 v 2.97 ± 0.26 mmol/kg dry weight, P < .05; 0.28 ± 0.07 v 0.45 ± 0.08 mmol/L intracellular water, P < .05); no increases were observed in the control subjects. Fasting dry-weight muscle lactate also increased post-dex only in the relatives (7.37 ± 0.40 v 10.77 ± 1.22 mmol/kg dry weight, P < .001). Both basal muscle glucose and lactate concentrations from the IVGTT study correlated with the 2-hour post-dex glucose value obtained during the OGTT study in the relatives (R = .76 and R = .74, respectively, both P < .0001) but not in the control subjects. Basal intramuscular glycogen synthase activity decreased approximately 25% in both the relatives and control subjects post-dex; the decrement was significant (P < .01) only in control subjects. Indirect calorimetry during the post-dex IVGTT demonstrated increased glucose oxidation (P < .03) and reduced lipid oxidation (P < .03) in the relatives only. We postulate that the insulin resistance induced by dex in first-degree relatives of type 2 diabetic patients is associated with a preferential channeling of glucose into the glycolytic pathway (increased glucose oxidation and lactate production), probably associated with a preexisting downregulation of the glycosen synthase pathway.

Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis.

The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6 +/- 0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3 +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n = 6). Administration of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2-response to reperfusion (n = 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.

Acute changes of systemic parameters in tumour-bearing rats, and of tumour glucose, lactate, and ATP levels upon local hyperthermia and/or hyperglycaemia

Arterial blood pressure and relevant parameters of the arterial blood (O2 and CO2 tensions, pH, haematocrit, serum electrolytes and osmolality) were determined in tumour-bearing rats upon local hyperthermia (HT) and/or hyperglycaemia (HG). Tumour heating was performed in a saline bath (44 degrees C) for 120 min; hyperglycaemia was induced by i.v. infusion of 40% glucose solution for 150 min [blood glucose levels: 35-40 mM during heating; total amount of glucose: 1.19 g/100 g body wt.; infusion rates: 0.31 ml (100 g body wt.)-1 min-1 for 2 min, 0.02 ml (100 g body wt.)-1 min-1 for 88 min, and 0.01 ml (100 g body wt.)-1 min-1 for 60 min]. Immediately after treatment, glucose, lactate and ATP levels were determined in tumour and muscle specimens and compared to these values under normothermic (NT) and/or normoglycaemic (NG) conditions. In all groups (NT/NG, NT/HG, HT/NG, HT/HG) there were only minor but characteristic changes in blood parameters, which were mainly due to the volume and type of the infused fluids (glucose solution, saline). During hyperglycaemia, tumour glucose levels rose 13- to 17-fold, whereas muscle glucose concentrations exhibited only a 3- to 5-fold increase; lactate levels were 1.9-2.5 times higher in tumours than in muscle, indicating an increase in the metabolic differences between normal and malignant tissues. Despite an increased glucose availability, tumours did not show an improved energy status and, thus, would not be expected to develop a decrease in thermal sensitivity or stimulation in growth rate. The good systemic tolerability of the combined treatment (HT/HG) and the differential changes in malignant and normal tissue occurring under these conditions, support further attempts to manipulate tumour metabolic environment by glucose in order to achieve better therapeutic results.

Anaerobic Swimming Metabolism of Fish: Sit-and-Wait versus Active Forager

The potential for generating energy during swimming via anaerobic metabolism and the ability to recover from exhaustive activity were examined in an actively foraging (creek chub, Semotilus atromaculatus) and a characteristically sit-and-wait species of fish (mudminnow, Umbra limi). The anaerobic threshold, as measured by a rise in muscle lactate, occurred at a higher swimming speed for the creek chub (~ 5 body lengths s⁻¹) than for the mudminnow (~2.0 body lengths s⁻¹). Anaerobic scope, defined as the rate of muscle-lactate production during maximal sprint activity, was 87% higher for the mudminnow (5.84 μmol g⁻¹ min⁻¹) than for the creek chub (3.13 μmol g⁻¹ min⁻¹). Whole-body anaerobic capacity at exhaustion (4 min) was also greater for mudminnows (9.82 μmol g⁻¹) than for creek chubs (6.46 μmol g⁻¹). The rate constant for muscle-lactate disappearance following exhaustion, however, was slightly higher for creek chubs (-0.63) than for mudminnows (-0.40). The time required for muscle-lactate concentration to return to resting values in these 1-2-g fish (4-6 h) was much less than previously reported times for large fish. Muscle-glucose concentration during recovery from 8 min of exhaustive activity was relatively unchanged in the creek chub but increased threefold in the mudminnow. The rate of increase in muscle-glycogen concentration following exhaustive activity was approximately sixfold higher for the mudminnow (23.6 mg [100 g]⁻¹ h⁻¹) than for the creek chub (3.7 mg [100 g]⁻¹ h⁻¹). Estimates of the time required for complete glycogen restoration were 6 h and 14 h for the mudminnow and creek chub, respectively. These results suggest that increased potential for and reliance on anaerobic energy production during swimming is characteristic of sit-and-wait foraging behavior in fish.

The influence of the relative proportions of dietary protein and carbohydrate on body weight gain, nitrogen retention and feed conversion of European eels, Anguilla anguilla L.

. Groups of European eels, Anguilla anguilla L., were fed on one of three diets, each at a different level of metabolic energy. These were constituted by combining 10%, 20% or 30% sucrose with 61%, 54% or 46% protein respectively. Eels fed a high percentage (30%) of sucrose grew faster than those on a high percentage of protein. Feed conversion and protein retention were higher for eels fed the high sucrose: low protein diet than for those fed with the lower proportions of sucrose. Blood plasma glucose concentration was higher in the elvers fed a high proportion of sucrose. However, the muscle glucose concentration was almost the same in ail experimental groups. Liver glycogen concentration was higher in elvers fed a high proportion of sucrose.

Effect of dietary carbohydrate source on soluble protein glucose concentration and enzyme activity (aldolase) of European eels ( Anguilla anguilla L.)

1. 1. This study was undertaken to determine the influence of dietary carbohydrate sources: wheat meal, bread meal, soluble corn starch, native potato starch and sorghum meal, on soluble protein, enzyme activity (aldolase) and glucose concentration in muscle and liver of European eels ( Anguilla anguilla). 2. 2. There was less soluble protein in both muscle and liver of eels fed 30% wheat meal or bread meal than the other experimental groups. 3. 3. However, eels fed 30% bread meal or soluble corn starch had a higher glucose concentration in muscle and liver than the other experimental groups. 4. 4. High enzyme activity (aldolase) was found in the liver of eels fed 30% wheat meal, bread meal or soluble starch.

Effect of tourniquet ischaemia on carbohydrate metabolism of dog skeletal muscle.

Metabolic changes in blood and skeletal muscle of dogs before, during and after tourniquet ischaemia were investigated to obtain further information on cellular metabolic abnormalities and restitution during and following long-lasting blood flow interruptions. Total carbohydrate and glycogen contents in the muscle tissue fell during ischaemia and remained significantly decreased even 1 h after recirculation due to inhibition of glycogen synthetase activity. Muscle glucose concentration remained stable during ischaemia and was significantly elevated 1 h after tourniquet release. In contrast, muscle lactate concentration was elevated during ischaemia and normal after recirculation. Blood lactate, pyruvate and serum inorganic phosphate concentrations increased markedly after tourniquet release and were still significantly elevated 1 h after recirculation, whereas ketone bodies and citric acid cycle intermediates remained unchanged. Tourniquet ischaemia had no effect on muscle phosphate concentration or on the activities of proteases, protease inhibitors or hydrolases in the blood. Nevertheless, our results clearly indicate metabolic abnormalities in the blood and skeletal muscle during 5 h of tourniquet ischaemia and even after 1 h of recirculation.