Effects of glucose ingestion or glucose infusion on fuel substrate kinetics during prolonged exercise

To determine if bypassing both intestinal absorption and hepatic glucose uptake by intravenous glucose infusion might increase the rate of muscle glucose oxidation above 1 g · min^–1, ten endurance-trained subjects were studied during 125 min of cycling at 70% of peak oxygen uptake (VO_{2 peak}). During exercise the subjects ingested either a 15 g · 100 ml^–1 U-¹⁴C labelled glucose solution or H₂O labelled with a U-¹⁴C glucose tracer for the determination of the rates of plasma glucose oxidation (Rox) and exogenous carbohydrate (CHO) oxidation from plasma¹⁴C glucose and¹⁴CO₂ specific activities, and respiratory gas exchange. Simultaneously, 2-³H glucose was infused at a constant rate to measure glucose turnover, while unlabelled glucose (25% dextrose) was infused into those subjects not ingesting glucose to maintain plasma glucose concentration at 5 mmol · l^–1. Despite similar plasma glucose concentrations [ingestion 5.3 (SEM 0.13) mmol · l^–1; infusion 5.0 (0.09) mmol · l^–1], compared to glucose infusion, CHO ingestion significantly increased plasma insulin concentrations [12.9 (1.0) vs 4.8 (0.5) mU · l^–1;P<0.05], raised total Rox values [9.5 (1.2) vs 6.2 (0.7) mmol · 125 min^–1 kg fat free mass^–1 (FFM);P<0.05] and rates of CHO oxidation [37.2 (2.8)vs 24.1 (3.9) mmol · 125 min^–1 kg FFM^–1;P<0.05]. An increased reliance on CHO metabolism with CHO ingestion was associated with a decrease in fat oxidation. Whereas the contribution from fat oxidation to energy production increased to 51 (10)% with glucose infusion, it only reached 18 (4)% with glucose ingestion (P<0.05). Despite these differences in plasma insulin concentration and rates of fat oxidation, the rates of glucose oxidation by muscle were similar after 125 min of exercise for both trials [ingestion 93 (8); infusion 85 (5) mol · min^–1 kg FFM^–1], suggesting that peak rates of muscle glucose oxidation were primarily dependent on blood glucose concentration which, in turn, regulated the hepatic appearance of ingested CHO.     

Exogenous carbohydrate oxidation from maltose and glucose ingested during prolonged exercise

Summary Intestinal perfusion studies have shown that glucose absorption from maltose occurs faster than from isocaloric glucose. To determine whether ingested maltose might be a superior source of carbohydrate (CHO) for endurance athletes, we compared the rates of gastric emptying, absorption and oxidation of 15 g · 100 ml^–1 solutions of maltose and glucose. Six endurance-trained cyclists drank 1200 ml of either U-¹⁴C maltose or U-¹⁴C glucose as a 400-ml loading bolus immediately before exercise, and as 8 × 100-ml drinks at 10-min intervals during a 90-min ride at 700% of maximal oxygen consumption. The rates of gastric emptying [maltose 690 (SD 119) ml · 90 min^–1; glucose 655 (SD 93) ml · 90 min^–1], the appearance of U-¹⁴C label in the plasma, and the peak rates of exogenous CHO oxidation [maltose 1.0 (SD 0.09) g · min^–1; glucose 0.9 (SD 0.09) g · min^–1] were not significantly different. Further, the 51 (SD 8) g of maltose and the 49 (SD 9) g of glucose oxidised during exercise were similar. Each accounted for approximately 2001o of the total CHO oxidised during the 90 min of exercise. Since only half of the CHO delivered to the intestine was oxidised in the 90-min ride (maltose 49%; glucose 50%), we conclude that neither the rate of gastric emptying, nor digestion limited the rate of ingested CHO utilisation during the early stages of exercise. Rather, we hypothesise that, initially, it could be the rate at which the CHO diffuses across the unstirred water layer of the brush-border of the intestinal villi that limits the utilisation of soluble CHO ingested during prolonged exercise.     

Fuel utilisation during prolonged low-to-moderate intensity exercise when ingesting water or carbohydrate

Previously, we examined the effects of carbohydrate (CHO) ingestion on glucose kinetics during exercise at 70% of maximum O₂ uptake ( O_2,max). Here we repeat those studies in heavier cyclists (n=6 per group) cycling for 3 h at a similar absolute O₂ uptake but at a lower (55% of O_2,max) relative exercise intensity. During exercise, the cyclists were infused with a 2-³H-glucose tracer and ingested U-¹⁴C glucoselabelled solutions of either flavoured water (H₂O) or 10 g/100 ml glucose polymer, at a rate of 600 ml/h. Two subjects in the H₂O trial fatigued after 2.5 h of exercise. Their rates of glucose appearance (R _a) declined from 2.9±0.6 to 2.0±0.1 mmol/min (mean ± SEM) and, as their plasma glucose concentration [Glu] declined from 4.7±0.2 to below 3.5±0.2 mM, their rates of glucose oxidation (R _ox) and fat oxidation plateaued at 2.7±0.4 and 1.7±0.1 mmol/min respectively. In contrast, all subjects completed the CHO trial. Although CHO ingestion during exercise reduced the final endogenousR _a from 3.4±0.6 to 0.9±0.3 mmol/min at the end of exercise, it increased totalR _a to 5.5±0.5 mmol/min (P<0.05). A higher totalR _a with CHO ingestion raised [Glu] from 4.3±0.3 to 5.3±0.1 mM and acceleratedR _ox from 3.5±0.2 to 5.9±0.2 mmol/min after 180 min of exercise (P<0.05). The increased contribution to total energy production from glucose oxidation (34±1 vs. 20±1 %) decreased energy production from fat oxidation from 51±2 to 40±5% (P=0.08) and produced patterns of glucose, muscle glycogen (plus lactate) and fat utilisation similar to those during exercise at 70% of ( O_2,max). Thus, CHO ingestion is necessary to sustain even prolonged, low to moderate intensity exercise and when ingested, it suppresses the higher relative rates of fat oxidation usually observed at exercise intensities less than 60% of O_2,max.     

Oxygen uptake kinetics during severe intensity running and cycling

The purpose of this study was to investigate the effect of exercise mode on the characteristics of the oxygen uptake ( V̇O₂) response to exercise within the severe intensity domain. Twelve participants each performed a treadmill running test and a cycle ergometer test to fatigue at intensities selected to elicit a mode-specific V̇O₂max and to cause fatigue in ~5 min. The tests were at 234 (30) m·min⁻¹ and 251 (59) W, and times to fatigue were 297 (15) s and 298 (14) s, respectively. The overall rapidity of the V̇O₂response was influenced by exercise mode [ V̇O₂max was achieved after 115 (20) s in running versus 207 (36) s in cycling; p<0.01]. V̇O₂ responses were fit to a three-phase exponential model. The time constant of the primary phase was faster in treadmill tests than in cycle ergometer tests [14 (6) s versus 25 (4) s; p<0.01], and the amplitude of the primary phase was greater in running than in cycling when it was expressed in absolute terms [2327 (393) ml·min⁻¹ versus 2036 (301) ml·min⁻¹; p=0.02] but not when it was expressed as a percentage of the total increase in V̇O₂ [86 (6)% versus 82 (6)%; p=0.09]. When quantified as the difference between the end-exercise V̇O₂ and the V̇O₂ at 2 min, the amplitude of the slow component was ~40% smaller in running [177 (92) ml·min⁻¹ versus 299 (153) ml min⁻¹; p=0.03]. It is concluded that exercise modality affects the characteristics of the V̇O₂ response at equivalent intensities in the severe domain.     

Study of Labeled Carbonate Metabolism in Healthy Organisms during Reparative Osteogenesis and Denervation by the Bone/Plasma Index

We studied the effect of mandibular fracture and denervation on [¹⁴C]carbonate metabolism. A new index (bone/plasma relative radioactivity) reflecting the ratio between ¹⁴C incorporation into bone and plasma was proposed. The percentage of label incorporation and bone/plasma relative radioactivity were measured from the 5th minute to the 192nd hour after intraperitoneal injection of labeled carbonate to 1-2-month-old albino rats. We revealed a biphasic reaction: rapid accumulation and elimination of the isotope form the bone; and slow accu-mulation followed by slow accumulation and elimination. Changes in carbonate metabolism after bone fracture corresponded to phases of reparative osteogenesis. At the stage of cellular-and-fibrous callus accumulation of labeled carbonate dominated over its elimination. At the stage of chondroid callus elimination dominated over accumulation. At the stage of primary osseous callus elimination dominated over accumulation, but did not surpass the control level. After fracture the index of bone/plasma relative radioactivity underwent general changes that were most pronounced in the zone of trauma. After denervation this index also decreased.     

Mapping of functional activity in the falcon visual system with [14C] 2-Deoxyglucose

Summary [¹⁴C] 2-Deoxyglucose uptake was mapped in the brain of one awake falcon which had one eye covered during the experiment, with the aim of providing tentative data on the identification of this bird's visual centers. Most of the structures with increased [¹⁴C] 2-Deoxyglucose uptake receive information from the exposed eye. Labeling was rather symmetrical in the hyperstriatum which receives bilateral projections from the visual thalamic centers.The results are largely consistent with what is known about the visual pathways in pigeons and owls. The falcon's visual Wulst as detected by the [¹⁴C] 2-Deoxyglucose labeling, is proportionally larger than that found in the pigeon. This result is consistent with the marked representation of the binocular visual field in the falcon's Wulst.Supported by grants 81/1138 of the Ministero delia Pubblica Istruzione and 82.00122.04 of the Consiglio Nazionale delle Ricerche     

Fuel substrate turnover and oxidation and glycogen sparing with carbohydrate ingestion in non-carbohydrate-loaded cyclists

This study examined the effects of ingesting 500 ml/h of either a 10% carbohydrate (CHO) drink (CI) or placebo (PI) on splanchnic glucose appearance rate (endogenous + exogenous) (R _a), plasma glucose oxidation and muscle glycogen utilisation in 17, non-carbohydrate-loaded, male, endurance-trained cyclists who rode for 180 min at 70% of maximum oxygen uptake. Mean muscle glycogen content at the start of exercise was 130 ± 6 mmol/kg ww; (mean ± SEM). Total CHO oxidation was similar in CI and PI subjects and declined during the trial. R _a increased significantly during the trial (P < 0.05) in both groups. Plasma glucose oxidation also increased significantly during the trial, reaching a plateau in the PI subjects, but was significantly (P < 0.05) higher in CI than PI subjects at the end of exercise [(98 ± 14 vs. 72 ± 10 μmol/min/kg fat-free mass) (FFM) (1.34 ± 0.19 vs. 0.93 ± 0.13 g/min)]. However, mean endogenous R _a was significantly (P < 0.05) lower in the CI than PI subjects throughout exercise (35 ± 7 vs. 54 ± 6 μmol/min/kg FFM), as was the oxidation of endogenous plasma glucose, which remained almost constant in CI subjects, and reached values at the end of exercise of 42 ± 13 and 72 ± 10 μmol/min/kg FFM in the CI and PI groups respectively. Of the 150 g CHO ingested during the trial, 50% was oxidised. Muscle glycogen disappearance was identical during the first 2 h of exercise in both groups and continued at the same rate in PI subjects, however no net muscle glycogen disappearance occurred during the final hour in CI subjects. We conclude that ingestion of 500 ml/h of a 10% CHO solution during prolonged exercise in non carbohydrate loaded subjects has a marked liver glycogen-sparing effect or causes a reduction in gluconeogenesis, or both, maintains plasma glucose concentration and has a muscle glycogen-sparing effect. Received: 25 August 1995/Received after revision: 25 March 1996/Accepted: 29 April 1996     

Labeled Citrate Metabolism in Bone Fractures and Impaired Innervation

Changes in ¹⁴C incorporation into regenerate after bone fracture and impairment of mandibular innervation, and injection of [3-¹⁴C]cytrate corresponded to the stages of reparative osteogenesis: after 1 week ¹⁴C incorporation in the cellular-fibrous callus surpassed its release, after 2 weeks the rates of ¹⁴C incorporation and release in the chondroid callus become similar, and after 4 weeks the release of the label predominated in the primary bone callus. Denervation reduced ¹⁴C incorporation into regenerate, which impaired bone remodeling. Citrate in the bones is characterized by high metabolic activity.     

Glucose kinetics during prolonged exercise in euglycaemic and hyperglycaemic subjects

To determine the limits to oxidation of exogenous glucose by skeletal muscle, the effects of euglycaemia (plasma glucose 5 mM, ET) and hyperglycaemia (plasma glucose 10 mM, HT) on fuel substrate kinetics were evaluated in 12 trained subjects cycling at 70% of maximal oxygen uptake (VO_{2, max}) for 2 h. During exercise, subjects ingested water labelled with traces of U-¹⁴C-glucose so that the rates of plasma glucose oxidation (R _ox) could be determined from plasma ¹⁴C-glucose and expired ¹⁴CO₂ radioactivities, and respiratory gas exchange. Simultaneously, 2-³H-glucose was infused at a constant rate to estimate rates of endogenous glucose turnover (R _a), while unlabelled glucose (25% dextrose) was infused to maintain plasma glucose concentration at either 5 or 10 mM. During ET, endogenous liver glucose R _a (total R _a minus the rate of infusion) declined from 22.4±4.9 to 6.5±1.4 mol/min per kg fat-free mass [FFM] (P<0.05) and during HT it was completely suppressed. In contrast, R _ox increased to 152±21 and 61±10 mol/min per kg FFM at the end of HT and ET respectively (P<0.05). HT (i. e., plasma glucose 10 mM) and hyperinsulinaemia (24.5±0.9 U/ml) also increased total carbohydrate oxidation from 203±7 (ET) to 310±3 mol/min per kg FFM (P<0.0001) and suppressed fat oxidation from 51±3 (ET) to 18±2 mol/min per kg FFM (P<0.0001). As the rates of oxidation at more physiological euglycaemic concentrations of glucose were limited to 92±9 mol/ min per kg FFM, and were similar to those reported when carbohydrate is ingested, the results of the current study suggest that the concentrations of glucose and insulin normally present during prolonged, intense exercise may limit the rate of muscle glucose uptake and oxidation.     

Myocardial oxygen supply and lactate metabolism during marked arterial hypoxaemia

Myocardial O₂ delivery and changes in myocardial lactate metabolism during marked hypoxaemia (pao₂ 5-5.4 kPa, Sa O₂ 70–75%) produced by 12% O₂ breathing were studied in 12 healthy subjects at rest and during supine exercise up to maximal intensity. Blood for O₂ and lactate analyses was sampled from catheters in an artery (a) and the coronary sinus (cs) and coronary sinus blood flow (CSBF) was measured by thermodilution. Lactate metabolism was evaluated in a subgroup of the subjects using i.v. infusion of [¹⁴C]lactate. At rest and during submaximal exercise up to heart rate 156 beats min^-1 myocardial O₂ uptake (MQO₂) was maintained at the same level during hypoxaemia as during normoxaemia. This was achieved at rest mainly by a more complete O₂ extraction, during exercise entirely by greater CSBF. During maximal exercise CSBF was 35% greater during hypoxaemia than normoxaemia, while there was no difference in cs O₂ saturation. Maximal MQO₂ was smaller during hypoxaemia than normoxaemia in spite of no difference in rate pressure product. The a-cs difference of lactate was reduced during hypoxaemia and there was a significant myocardial release of lactate, as calculated from [¹⁴C]lactate data, during hypoxaemic exercise, but not during hypoxaemic rest or normoxaemic rest and exercise. It is concluded that the heart has a coronary flow reserve of about 35%, which can be utilised under hypoxaemia. When this reserve is insufficient to supply the myocardium with oxygen lactate is produced to cover part of the myocardial ATP regeneration.     

Histoautoradiographic study of [3H]thymidine uptake into parenchymal nuclei of the kidney and other organs in rats with nephrotoxic nephritis

Data were obtained to show how changes in the [³H]thymidine uptake by parenchymal nuclei of the kidney compare with those in other organs in rats with nephrotoxic nephritis. The labeling index in the kidneys increased: by 7.5 times in the epithelial cells of the renal cortex and by 15 times in the epithelium of the medulla. The number of labeled cells in the glomeruli increased by 2.5 times. The labeling index in the epithelium of the adrenals, liver, thymus, and small intestine fell to between 80 and 70% of normal.Central Scientific-Research Laboratory, Central Postgraduate Medical Institute, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 612–614, June, 1979.     

Autoradiographic analysis of RNA synthesis by sympathetic neurons in a population containing a reduced number of cells

An autoradiographic analysis was made of the dynamics of synthesis of nuclear and cytoplasmic RNA by sympathetic neurons of presenile mice subjected to partial desympathization during the first days after birth by injection of guanethidine. Neurons from a population with a sharply reduced number of cells have lower rates of migration of newly synthesized RNA from nucleus into cytoplasm than in the corresponding age control. Neurons of partially desympathized animals of infantile, juvenile, and presenile ages are no larger than the cell bodies of control mice.Department of Biology, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupruyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 746–748, June, 1977.     

Glucagon receptors along the nephron: [125I]glucagon binding in rat tubules

Binding of [¹²⁵I]glucagon was measured in microdissected pieces of tubules from the rat nephron. Specific glucagon binding sites were found only in nephron segments containing a glucagon-sensititive adenylate cyclase activity. At 7.5 nM labelled hormone, higher levels of specific binding (16–27×10^–18 mol mm^–1) were found in the thick ascending limb of the Henle's loop and in the distal convoluted tubule and lower binding levels (2–5×10^–18 mol mm^–) in the collecting tubule whereas specific binding could not be detected in the proximal tubule and in the thin segments of the Henle's loop. In the medullary thick ascending limb, Scatchard analysis of specific [¹²⁵I]glucagon binding indicated an apparent equilibrium dissociation constant of 2.4 nM. The stereospecificity of binding sites in medullary thick ascending limbs and medullary collecting tubules, was assessed by competition experiments using unlabelled glucagon, enteroglucagon and unrelated hormones (vasopressin, calcitonin, parathyroid hormone and insulin); in both segments, glucagon was more active than enteroglucagon in displacing labelled glucagon from its tubular binding sites, whereas all other hormones tested were inactive. These results indicate that tubule binding sites might be the physiological receptors for glucagon involved in adenylate cyclase activation.Abbreviations PCT proximal convoluted tubule - TDL thin descending limb - TAL thin ascending limb - MAL medullary thick ascending limb - CAL cortical ascending limb - DCT distal convoluted tubule - CCT cortical collecting tubule - MCT medullary collecting tubule     

[51Cr]EDTA for measuring total and single nephron glomerular filtration rate in the rat

Clearance and micropuncture experiments were performed in halothane anaesthetized rats. The aim was a comparison of paired estimates of glomerular filtration rate (GFR) from the renal clearance of [⁵¹Cr]EDTA (C_[51Cr]EDTA) with simultaneous estimates of polyfructosan ((Inutest) C_In), ³H,- and ¹⁴C-labelled inulin clearance (C_[3H]In and C_[14C]In, respectively) and proximal tubular fluid/plasma concentration ratios (TF/P) of [¹⁵Cr]EDTA and TF/P ratios of ¹⁴C-labelled inulin measured in the same samples. C_[51Cr]EDTA correlated well with, but underestimated C_In by ? 10%. The correlation coefficient (r) was 0.92. C_[51.Cr]EDTA also correlated with, and underestimated C_[14C]In by 6%, r= 0.88, whereas it overestimated C_[3H]In by 5%, still with a close correlation (r= 0.92). Paired data on proximal (TF/P) ratios of [¹⁵Cr]EDTA and [¹⁴C]inulin were collected from early, mid and late proximal convolutions. The data were scattered around the line of identity, r= 0.91. It is concluded that [¹⁵Cr]EDTA is a valid alternative for estimates of total renal and single nephron GFR in rats and has the advantage of being less expensive than [¹⁴C]inulin.     

14C-histamine release during vasodilatation induced by lumbar ventral root stimulation

Summary The vascularly isolated hindlimbs of dogs under chloralose anesthesia and neuromuscular blockade were perfused at constant flow with the animal's own arterial blood. Stimulation of the spinal ventral roots from L₅ to L₇ induced an antihistamine sensitive vasodilatation (VD) in the ipsilateral limb [Graham, Lioy: Histaminergic vasodilatation in the hindlimb of the dog. Pflügers Arch.342, 307–318 (1973)]. One hundred C of¹⁴C-histidine were injected into the limb perfusion line. Endogenously formed¹⁴C-histamine increased in the femoral venous blood from 59.2±17.0 to 190.3±41.9 cpm/ml of blood (P<0.005) during the VD induced by ventral root stimulation, while¹⁴C-histidine kept decreasing during the periods of observation. A significant increase of labeled histamine was also present upon ventral root stimulation after the VD had been drastically reduced or abolished by mepyramine maleate. It is concluded that the hindlimb VD under study is due to the nervously mediated release of histamine.     

Response of the pituitary-adrenocortical system to prolonged action of small doses released from an internal depot of [75Se] selenomethionine

The principles governing the distribution of the absorbed dose and the dynamics of its formation were studied by a radiometric technique in vivo during the course of 1 year after injection of 0.033 Ci/g of [⁷⁵Se] selenomethionine into rats and the functional state of the pituitary-adrenal adaptive system was studied at the same time by determination of the plasma corticosterone level. The preparation was shown to have high affinity for the organs of the endocrine system. Evidence of increased functional activity of the adaptation system was given by an increase in the corticosterone concentration in the animals' blood plasma after injection of the radioactive preparation, which was significantly higher than in the control 3, 6, and 10 months after the beginning of the experiments. Exposure to acute stress (induced by histamine and formalin) 10 months after injection of [⁷⁵Se] selenomethionine did not produce the sharp increase in the plasma corticosterone concentration characteristic of the control rats; this points to extreme stress of the pituitary-adrenal system and its inability to respond to additional loads. It is postulated that analysis of the functional state of the adaptation system could provide the key to the assessment of the biological effect of small doses of radiation.Institute of Medical Radiology, Academy of Medical Sciences of the USSR, Obninsk. (Presented by Academician of the Academy of Medical Sciences of the USSR G. A. Zedgenidze.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 20–23, January, 1978.