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Currently there is great interest in developing cytotoxic pharmacotherapies that disrupt mitochondrial energy transduction in cancer. Given that mitochondria are critical to mammalian energy homeostasis, clinical success of a given therapeutic will undoubtedly hinge upon its cancer cell selectivity. That said, how the mitochondrial network is intrinsically remodeled to drive/enable the cancer phenotype remains a biological black box, largely due to limitations in analytical approaches. Herein, we leveraged an in-house diagnostic biochemical workflow to comprehensively evaluate mitochondrial bioenergetic efficiency and capacity in human leukemia. Using this platform, we provide direct evidence that despite minimal changes in absolute respiratory kinetics, leukemic mitochondria are hallmarked by intrinsic limitations in oxidative phosphorylation (OXPHOS) that constrain the network’s ability to contribute to cellular ATP free energy (i.e, ΔGATP) charge. Together, these findings link accelerated oxidative metabolism in leukemia to intrinsic OXPHOS deficiency and provide proof-of-concept that restoring, rather than disrupting, OXPHOS across the leukemic mitochondrial network may represent an untapped, but highly feasible, therapeutic avenue.

The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of this study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved. Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24-h lipid incubation. Mitochondrial respiration (state 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost twofold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24-h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P

Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis. A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology. Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondrial hydrogen peroxide (H2O2) emission and a shift to a more oxidized intracellular redox environment. Blocking H2O2 emission prevents the shift in redox environment and preserves insulin sensitivity, providing evidence that the mitochondrial respiratory system is able to sense and respond to cellular metabolic imbalance. Mitochondrial H2O2 emission is a major regulator of protein redox state, as well as the overall cellular redox environment, raising the intriguing possibility that elevated H2O2 emission from nutrient overload may represent the underlying basis for the development of insulin resistance due to disruption of normal redox control mechanisms regulating protein function, including the insulin signaling and glucose transport processes.

Bendavia is a mitochondria-targeting peptide currently being tested in the EMBRACE-STEMI trial for reducing injury during acute coronary syndromes. We previously showed that the cardioprotective effects of Bendavia involved improving cardiolipin-dependent mitochondrial membrane fluidity. As membrane fluidity influences the ability of proteins to assemble, we hypothesized that a consequence of augmented membrane fluidity would be higher expression of mitochondrial respiratory supercomplexes. Rat hearts (n=42) were subjected to ischemia-reperfusion (I/R) with or without 1nM Bendavia perfusion beginning at the onset of reperfusion. Left ventricular tissue was split into one of two study arms: 1. Supercomplex expression using blue-native gel electrophoresis (BN-PAGE), or 2. High-resolution respirometry using permeabilized ventricular fibers. For BN-PAGE studies, respiratory supercomplex bands were decreased with I/R, and restored with Bendavia (see figure). High-resolution respirometry studies indicated suppressed Complex I-dependent respiration after I/R (208±19 v 42±9 pmol O2/mg*s in control v I/R, respectively; P

The purpose of the present study was to test the suitability of the rat hindlimb perfusion technique for studying the acute regulation of the GLUT-1 and GLUT-4 glucose transporter genes in adult skeletal muscle. To further examine the stability of the technique, we also monitored the transcription rate and mRNA content of selected immediate early genes. Nuclei and total RNA were isolated from red and white hindlimb muscle from perfused (2 h) and nonperfused control animals. Although GLUT-4 transcription and mRNA content remained stable, perfusion elicited a marked 3.5-fold increase in GLUT-1 mRNA in red and 2.2-fold increase in white skeletal muscle in the absence of any detectable change in transcription. In contrast to both GLUT-1 and GLUT-4, transcription originating from the c-fos and c-myc immediate early genes increased from 2.0- to 2.7-fold with perfusion in both red and white skeletal muscle, whereas transcription of the beta-actin gene decreased by 40-60%. Both c-fos and c-myc mRNA levels also increased with perfusion, whereas beta-actin mRNA remained unchanged. These findings clearly demonstrate that the current method of performing the hindlimb perfusion technique rapidly and dramatically alters the regulation of selected genes in skeletal muscle.

Heart fatty acid-binding protein (H-FABP) is present in a wide variety of tissues but is found in the highest concentration in cardiac and red skeletal muscle. It has been proposed that the expression of H-FABP correlates directly with the fatty acid-oxidative capacity of the tissue. In the present study, the expression of H-FABP was measured in red and white skeletal muscle under two conditions in which fatty acid utilization is known to be increased: streptozotocin-induced diabetes and fasting. Protein concentration, mRNA concentration and transcription rate were measured under both conditions. The level of both protein and mRNA increased approximately 2-fold under each condition. The transcription rate was higher in red skeletal muscle than in white muscle, was increased 2-fold during fasting, but was unchanged by streptozotocin-induced diabetes. In addition to supporting the hypothesis that H-FABP is induced during conditions of increased fatty acid utilization, these findings demonstrate that the regulation of H-FABP expression may or may not be at the level of transcription depending on the stimulus.

Endurance exercise training elicits an increase in mitochondrial density as well as GLUT-4 glucose transporter protein content in skeletal muscle. Corresponding increases in mRNA for respiratory enzymes and GLUT-4 indicate that pretranslational control mechanisms are involved in this adaptive process. To directly test whether transcription of the GLUT-4 gene is activated in response to exercise training, nuclei were isolated from red hindlimb skeletal muscle of rats after 1 wk of exercise training (8% grade, 32 m/min, 40 min, twice/day). Rats were killed either 30 min, 3 h, or 24 h after the last training session. GLUT-4 transcription, determined by nuclear run-on analysis, was unaltered after 30 min, increased by 1.8-fold after 3 h, but was no longer different from controls 24 h after exercise. A similar transient increase in GLUT-4 transcription was evident, but less pronounced (1.4-fold), in untrained rats after a single bout of exercise, suggesting that the postexercise induction in GLUT-4 gene transcription is enhanced by exercise training. GLUT-4 protein content was increased 1.7-fold after 1 wk of training in the absence of any corresponding change in GLUT-4 mRNA, providing evidence that the initial increase in GLUT-4 expression involves translational and/or posttranslational control mechanisms. These findings demonstrate that muscle GLUT-4 expression in response to exercise training is subject to both transcriptional and posttranscriptional regulation. We propose that the increase in GLUT-4 mRNA evident with extended periods of training may result from a shift to pretranslational control and is the cumulative effect of repeated postexercise transient increases in GLUT-4 gene transcription.

This investigation studied the importance of the rise in body temperature during exercise for aerobic capacity adaptations produced by endurance training. The approach used was to compare training effects produced by subjects exercising in hot (35 degrees C) water vs. cold (20 degrees C) water. Hot water was used to potentiate, and cold water to blunt, the rise in body temperature during exercise. Eighteen young men trained by cycle-ergometer exercise at 60% of maximal oxygen uptake (VO2max) while immersed to the neck in either hot (HWT, n = 9) or cold (CWT, n = 9) water for 60 min, 5 days/wk, for 8 wk. Before and after training, VO2max, erythrocyte volume, plasma volume, and vastus lateralis citrate synthase activity were measured. Training increased (P < 0.01) VO2max by 13%, with no difference between HWT and CWT in the magnitude of the effect. Erythrocyte volume increased 4% (P < 0.01) with training, with no difference between HWT and CWT in the magnitude of the effect. Plasma volume remained unchanged by training in both the HWT and CWT groups. Last, vastus lateralis citrate synthase activity increased by 38% with training, but there was no difference between HWT and CWT in the training effect. Thus, exercise-induced body temperature elevations are not an important stimulus for the aerobic adaptations to moderate-intensity endurance training.

GLUT4 glucose transporter protein and mRNA levels in rat skeletal muscle are decreased with streptozotocin (STZ)-induced diabetes and increased by fasting, indicating that GLUT4 expression may be regulated at the pretranslational level. The purpose of the present study was to determine whether GLUT4 is subject to transcriptional regulation in skeletal muscle under the altered metabolic conditions of diabetes and fasting. Nuclei were isolated from red and white portions of the quadriceps and gastrocnemius/plantaris muscles of control, 7-day STZ-diabetic, and 3-day fasted rats. STZ-induced diabetes resulted in a 35% reduction in GLUT4 transcription in red skeletal muscle and thus accounted for a major portion of the corresponding 50% reduction in GLUT4 mRNA observed in red skeletal muscle. STZ-induced diabetes had no significant effect on GLUT4 transcription or mRNA in white skeletal muscle. Fasting, however, significantly increased both GLUT4 transcription (2.2-fold) and mRNA (2.9-fold) in white skeletal muscle with no change detected for either parameter in red skeletal muscle. The nearly 2-fold higher steady-state GLUT4 mRNA in red versus white skeletal muscle of control rats was not associated with any difference in basal transcription. These findings demonstrate that expression of the GLUT4 glucose transporter protein in skeletal muscle is subject to regulation in vivo at the level of transcription of the GLUT4 gene. In addition, GLUT4 transcription is regulated in a fiber type-specific manner in response to the metabolic challenges elicited by STZ-induced diabetes and fasting.

We examined glucose uptake and GLUT-4 in rat muscles [soleus (Sol), plantaris (PL), extensor digitorum longus (EDL), tibialis anterior, and the red and white gastrocnemius (WG)]. In the normally innervated perfused rat hindlimb muscles the proportion of oxidative fibers was highly correlated with the muscle's insulin-stimulated 3-O-methyl-D-glucose (3-MG) uptake (R2 = 0.78) and GLUT-4 content (r = 0.94). Insulin-stimulated 3-MG uptake and GLUT-4 were also highly correlated (R2 = 0.996). In 3-day denervated muscles, insulin-stimulated 3-MG uptake was reduced in all six muscles (-41 to -14.6%, P < 0.05), and GLUT-4 content was also reduced (-87.5 to -34.9%), except in the WG and EDL (P > 0.05). A very high correlation was observed between the decrements in GLUT-4 (%) and the decrements in 3-MG uptake (%; r = 0.99). The relatively greater loss in muscle activity (%) due to denervation in the Sol compared with the PL coincided with the reductions (%) in GLUT-4 and 3-MG uptake. These studies demonstrate that glucose uptake and GLUT-4 are regulated by insulin-independent means, namely the oxidative capacity of the muscle and the normal activity level of the muscle.

The purpose of this study was to determine whether short-term training cessation resulted in reduced GLUT-4 protein levels. Endurance- (n = 12, ET) and strength-trained (n = 12) individuals (ST) were examined before and after 14 days of training withdrawal. GLUT-4 content was determined from muscle biopsy samples of the gastrocnemius in ET and the vastus lateralis in ST. Insulin sensitivity (oral glucose tolerance test) was significantly (P < 0.05) reduced in ET and ST with training cessation. GLUT-4 content was unaltered (P > 0.05) in both groups (92 and 100% of trained values for ET and ST, respectively). In ET, citrate synthase activity decreased significantly (P < 0.05) with training withdrawal (41.0 +/- 3.6 vs. 30.6 +/- 2.8 mumol.g-1.min-1); in ST no change was evident. The decrement in insulin sensitivity with the cessation of endurance- or resistance-oriented activity is therefore not associated with a reduction in GLUT-4 protein content. Muscle oxidative capacity and GLUT-4 content do not coincide with the removal of endurance training.

Context: In lean individuals, increasing dietary lipid can elicit an increase in whole body lipid oxidation; however, with obesity the capacity to respond to changes in substrate availability appears to be compromised. Objective: To determine whether the responses of genes regulating lipid oxidation in skeletal muscle differed between lean and insulin resistant obese humans upon exposure to a high-fat diet (HFD). Design and Setting: A 5-d prospective study conducted in the research unit of an academic center. Participants: Healthy, lean (n = 12; body mass index = 22.1 ± 0.6 kg/m2), and obese (n=10; body mass index = 39.6 ± 1.7 kg/m2) males and females, between ages 18 and 30. Intervention: Participants were studied before and after a 5-d HFD (65% fat). Main Outcome Measures: Skeletal muscle biopsies (vastus lateralis) were obtained in the fasted and fed states before and after the HFD and mRNA content for genes involved with lipid oxidation determined. Skeletal muscle acylcarnitine content was determined in the fed states before and after the HFD. Results: Peroxisome proliferator activated receptor (PPAR) α mRNA content increased in lean, but not obese, subjects after a single high-fat meal. From Pre- to Post-HFD, mRNA content exhibited a body size × HFD interaction, where the lean individuals increased while the obese individuals decreased mRNA content for pyruvate dehydrogenase kinase 4, uncoupling protein 3, PPARα, and PPARγ coactivator-1α (P ≤ 0.05). In the obese subjects medium-chain acylcarnitine species tended to accumulate, whereas no change or a reduction was evident in the lean individuals. Conclusions: These findings indicate a differential response to a lipid stimulus in the skeletal muscle of lean and insulin resistant obese humans.

This study determined whether 1) exhaustion from heat strain occurs at the same body temperatures during exercise in the heat when subjects are euhydrated as when they are hypohydrated, 2) aerobic fitness influences the body temperature at which exhaustion from heat strain occurs, and 3) curves could be developed to estimate exhaustion rates at a given level of physiological strain. Seventeen heat-acclimated men [maximal oxygen uptake (VO2max) from 45 to 65 ml.kg-1.min-1] attempted two heat stress tests (HSTs): one when euhydrated and one when hypohydrated by 8% of total body water. The HSTs consisted of 180 min of rest and treadmill walking (45% VO2max) in a hot-dry (ambient temperature 49 degrees C, relative humidity 20%) environment. The required evaporative cooling (Ereq) exceeded the maximal evaporative cooling capacity of the environment (Emax); thus thermal equilibrium could not be achieved and 27 of 34 HSTs ended by exhaustion from heat strain. Our findings concerning exhaustion from heat strain are 1) hypohydration reduced the core temperature that could be tolerated; 2) aerobic fitness, per se, did not influence the magnitude of heat strain that could be tolerated; 3) curves can be developed to estimate exhaustion rates for a given level of physiological strain; and 4) exhaustion was rarely associated with a core temperature up to 38 degrees C, and it always occurred before a temperature of 40 degrees C was achieved. These findings are applicable to heat-acclimated individuals performing moderate-intensity exercise under conditions where Ereq approximates or exceeds Emax and who have high skin temperatures.

The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.

Fasting elicits a progressive increase in lipid metabolism within skeletal muscle. To determine the effects of fasting on the transcriptional regulation of genes important for metabolic control in skeletal muscle composed of different fiber types, nuclei from control and fasted (24 and 72 h) rats were subjected to nuclear run-on analysis using an RT-PCR-based technique. Fasting increased ( P < 0.05) transcription rate of the muscle-specific uncoupling protein-3 gene (UCP3) 14.3- to 21.1-fold in white gastrocnemius (WG; fast-twitch glycolytic) and 5.5- to 7.5-fold in red gastrocnemius (RG; fast-twitch oxidative) and plantaris (PL; mixed) muscles. No change occurred in soleus (slow-twitch oxidative) muscle. Fasting also increased transcription rate of the lipoprotein lipase (LPL), muscle carnitine palmitoyltransferase I (CPT I), and long-chain acyl-CoA dehydrogenase (LCAD) genes 1.7- to 3.7-fold in WG, RG, and PL muscles. Transcription rate responses were similar after 24 and 72 h of fasting. Surprisingly, increasing metabolic demand during the initial 8 h of starvation (two 2-h bouts of treadmill running) attenuated the 24-h fasting-induced transcriptional activation of UCP3, LPL, CPT I, and LCAD in RG and PL muscles, suggesting the presence of opposing regulatory mechanisms. These data demonstrate that fasting elicits a fiber type-specific coordinate increase in the transcription rate of several genes involved in and/or required for lipid metabolism and indicate that exercise may attenuate the fasting-induced transcriptional activation of specific metabolic genes.

Continuous contractile activity of skeletal muscle elicits an early and dramatic increase in ribosomal RNA, suggesting that translational efficiency and/or capacity is enhanced during the adaptive response to increased metabolic demand. In view of the important role heat shock or stress proteins (HSPs) play as molecular chaperones during protein synthesis, we examined whether expression of the inducible 70-kDa HSP (HSP70) and/or mitochondrial 60-kDa HSP (HSP60) is altered in rabbit tibialis anterior muscle during continuous low-frequency motor nerve stimulation. Induction of the HSP70 gene was evident within 24 h after the onset of stimulation as reflected by increases in HSP70 transcription (> 20-fold) and mRNA (> 50-fold). HSP70 protein levels were significantly elevated (10- to 12-fold) after 14 and 21 days of stimulation. Mitochondrial HSP60 mRNA and protein also increased during stimulation (> 18- and > 5-fold after 21 days, respectively). In situ hybridization and immunohistochemistry coupled with myosin ATPase staining revealed that expression of HSP70 was restricted to oxidative type I and IIa fibers during the first 3 days of stimulation but shifted to primarily type II fibers after 21 days of stimulation. These findings demonstrate that induction of HSP70 during the adaptive response to chronic motor nerve stimulation proceeds from type I/IIa to type IId(x)/b fibers, suggesting that the expression of HSPs may be required to support the folding and compartmentalization of nascent proteins during the transformation process.

AlphaB-crystallin (alphaBC) is a major structural protein (22 kDa) of the ocular lens as well as a bona fide heat shock protein in non-lens tissue. The alphaBC gene is abundantly expressed in tissues with high oxidative capacity, including the heart and type I skeletal muscle fibers, and is regulated by the MyoD family of basic helix-loop-helix transcription factors during myogenesis. To test the hypothesis that alphaBC expression may be directly regulated by the demand for oxidative metabolism, we examined the expression of alphaBC and the ancestral-related Hsp27 in rabbit tibialis anterior muscle subjected to continuous low frequency motor nerve stimulation (3 V, 10 Hz). alphaBC mRNA and protein increased within the 1st day of continuous contractile activity (5- and 2.5-fold, respectively) and achieved maximum levels (20-and 4-fold, respectively) after 21 d of stimulation. Hsp27 mRNA and protein levels also increased with stimulation, but with a less specific and dramatic induction pattern. In agreement with the Northern analysis, in situ hybridization performed on cross sections from tibialis anterior muscle revealed progressively increasing alphaBC transcript signal, localized in a ringlet pattern, from 1 through 21 days of stimulation. Serial sections subjected to myosin immunohistochemistry revealed that alphaBC expression was confined to slow-twitch type I and a subpopulation of fast twitch type II fibers after 1 day but present in nearly all fibers after 21 days of stimulation. Transcript levels of all four myogenic regulatory factors (MyoD, myogenin, myf-5, and MRF4) also increased with stimulation in a pattern temporally similar with alphaBC, suggesting that expression of alphaBC in response to stimulation may, in part, be regulated through myogenic regulatory factor(s) interaction with the canonical E-box element located within the alphaBC promotor. These data demonstrate that expression of the small heat shock protein, alphaBC, is rapidly induced independent of the ancestrally related Hsp27 in a fiber type specific pattern in skeletal muscle subjected to the oxidative stress imposed by continuous contractile activity.

Recent progress in defining molecular components of pathways controlling early stages of myogenesis has been substantial, but regulatory factors that govern the striking functional specialization of adult skeletal muscle fibers in vertebrate organisms have not yet been identified. A more detailed understanding of the temporal and spatial patterns by which specialized fiber characteristics arise may provide clues to the identity of the relevant regulatory factors. In this study, we used immunohistochemical, in situ hybridization, and Northern blot analyses to examine the time course and spatial characteristics of expression of myoglobin protein and mRNA during development of the distal hindlimb in the mouse. In adult animals, myoglobin is expressed selectively in oxidative, mitochondria-rich, fatigue-resistant myofibers, and it provides a convenient marker for this particular subset of specialized fibers. We observed only minimal expression of myoglobin in the hindlimb prior to the second day after birth, but a rapid and large (50-fold) induction of this gene in the ensuing neonatal period. Myoglobin expression was limited, however, to fibers located centrally within the limb which coexpress myosin isoforms characteristic of type I, IIA, and IIX fibers. This induction of myoglobin expression within the early postnatal period was accompanied by increased expression of nuclear genes encoding mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial protein expression that can be induced in adult muscle fibers by continuous motor nerve stimulation. This comparison suggests that progressive locomotor activity of neonatal animals may provide signals which trigger the development of the specialized features of oxidative, fatigue-resistant skeletal muscle fibers.

The derivation of human cell lines devoid of mitochondrial (mt) DNA (rho 0) provides an opportunity to study nuclear responses to a chronic impairment of mitochondrial oxidative phosphorylation. Expression of several nuclear genes is induced in human rho 0 cells, including those encoding integral proteins of the mitochondrial inner membrane, intermediate filaments, and ribosomes. In contrast to conditions in which mitochondrial respiration is altered acutely, expression of heat shock proteins and immediate early genes is not induced. Mitochondria from rho 0 cells maintain a transmembrane electrochemical potential and are distributed within the cytoplasm of these cells in a manner indistinguishable from that of wild-type cells. We conclude that a chronic deficiency of mitochondrial oxidative phosphorylation produced by elimination of mtDNA is associated with a different pattern of gene induction than that provoked by other acute or subacute conditions that impair mitochondrial respiration or create energy demands in excess of mitochondrial respiratory capacity.

GLUT4 glucose transporter protein and mRNA levels in rat skeletal muscle are decreased with streptozotocin (STZ)-induced diabetes and increased by fasting, indicating that GLUT4 expression may be regulated at the pretranslational level. The purpose of the present study was to determine whether GLUT4 is subject to transcriptional regulation in skeletal muscle under the altered metabolic conditions of diabetes and fasting. Nuclei were isolated from red and white portions of the quadriceps and gastrocnemius/plantaris muscles of control, 7-day STZ-diabetic, and 3-day fasted rats. STZ-induced diabetes resulted in a 35% reduction in GLUT4 transcription in red skeletal muscle and thus accounted for a major portion of the corresponding 50% reduction in GLUT4 mRNA observed in red skeletal muscle. STZ-induced diabetes had no significant effect on GLUT4 transcription or mRNA in white skeletal muscle. Fasting, however, significantly increased both GLUT4 transcription (2.2-fold) and mRNA (2.9-fold) in white skeletal muscle with no change detected for either parameter in red skeletal muscle. The nearly 2-fold higher steady-state GLUT4 mRNA in red versus white skeletal muscle of control rats was not associated with any difference in basal transcription. These findings demonstrate that expression of the GLUT4 glucose transporter protein in skeletal muscle is subject to regulation in vivo at the level of transcription of the GLUT4 gene. In addition, GLUT4 transcription is regulated in a fiber type-specific manner in response to the metabolic challenges elicited by STZ-induced diabetes and fasting.

Exercise training has been proposed to improve whole body insulin sensitivity through a postreceptor adaptation in skeletal muscle. This study examined if levels of the insulin-responsive muscle glucose transporter protein (GLUT-4) were associated with improved insulin sensitivity in trained vs. sedentary middle-aged individuals. Muscle GLUT-4 levels and oral glucose tolerance test (OGTT) responses were obtained in age-matched trained and sedentary men (n = 11). Plasma insulin levels during the OGTT were significantly lower (P less than 0.01) in the trained men, whereas no differences were seen in plasma glucose responses. GLUT-4 protein content was approximately twofold higher in the trained men (2.41 +/- 0.17 vs. 1.36 +/- 0.11 micrograms standard, P less than 0.001). OGTT responses and GLUT-4 levels were not altered 15-18 h after a standard exercise bout in six representative sedentary subjects. These data suggest that GLUT-4 levels are increased in conjunction with insulin sensitivity in chronically exercise-trained middle-aged men. This finding suggests a possible mechanism for the improved insulin sensitivity observed with exercise training in humans.

This study examined the thermoregulatory and hydrational status of men during sustained activity in a hot-dry (37 degrees C, 20% rh) environment while they consumed only a nutrient solution (nutrient), or consumed only colored, flavored water (control). Eleven heat acclimated young men attempted 24-h sustained activity experiments. These experiments consisted of alternating 45-min bouts of treadmill walking (410 W, approximately 30% VO2max) and rest (including sedentary activity). Data were analyzed through 13 h (after 13 h subjects began to discontinue testing). No significant differences between trials were observed for metabolic rate, fluid intake, skin or rectal temperature, sweating rate, plasma volume (as indicated by hemoglobin concentration) or plasma glucose concentrations. By the 8th h plasma osmolality was higher and by the 11th h plasma free fatty acids were lower during the nutrient trial compared to the control. In separate experiments with nine different men, the gastric emptying rates of the nutrient solution and water were compared during exercise (55% VO2max) in the heat (35 degrees C, 20% rh). The gastric emptying rates of the nutrient solution and water were similar (approximately 20 ml.min-1). These data indicate that during 13 h of sustained activity in a hot environment, the nutrient solution and water provided similar thermoregulatory and hydrational benefits.

With the cessation of exercise, glycogen repletion begins to take place rapidly in skeletal muscle and can result in glycogen levels higher than those present before exercise. Understanding the rate-limiting steps that regulate glycogen synthesis will provide us with strategies to increase the resynthesis of glycogen during recovery from exercise, and thus improve performance. Given the importance of muscle glycogen to endurance performance, various factors which may optimise glycogen resynthesis rate and insure complete restoration have been of interest to both the scientist and athlete. The time required for complete muscle glycogen resynthesis after prolonged moderate intensity exercise is generally considered to be 24 hours provided approximately 500 to 700g of carbohydrate is ingested. Muscle glycogen synthesis rate is highest during the first 2 hours after exercise. Ingestion of 0.70g glucose/kg bodyweight every 2 hours appears to maximise glycogen resynthesis rate at approximately 5 to 6 mumol/g wet weight/h during the first 4 to 6 hours after exhaustive exercise. Further enhancement of glycogen resynthesis rate with ingestion of greater than 0.70g glucose/kg bodyweight appears to be limited by the constraints imposed by gastric emptying. Ingestion of glucose or sucrose results in similar muscle glycogen resynthesis rates while glycogen synthesis in liver is better served with the ingestion of fructose. Also, increases in muscle glycogen content during the first 4 to 6 hours after exercise are greater with ingestion of simple as compared with complex carbohydrate. Glycogen synthase activity is a key component in the regulation of glycogen resynthesis. Glycogen synthase enzyme exists in 2 states: the less active, more phosphorylated (D) form which is under allosteric control of glucose-6-phosphate, and the more active, less phosphorylated (I) form which is independent of glucose-6-phosphate. There is generally an inverse relationship between glycogen content in muscle and the percentage synthase in the activated (I) form. Exercise and insulin by themselves activate glycogen synthase by conversion to glycogen synthase I. Although small changes in the activity ratio (% I form) can lead to large changes in the rate of glycogen synthesis, glycogen synthase I appears to increase very little (approximately 25%) in response to glycogen depletion and returns to pre-exercise levels as glycogen levels return to normal. Thus glycogen resynthesis, which may increase 3- to 5-fold, may also be influenced by glucose-6-phosphate, which can activate glycogen synthase in the D form.(ABSTRACT TRUNCATED AT 400 WORDS)

The purpose of this study was to compare gastric emptying (GE) responses during intense, prolonged cycling and running. It is important to discern whether gastric emptying (GE) responses are exercise-mode specific, since the findings of cycling and running studies are often compared and applied to one another. Ten male biathletes cycled (CY) and ran (R) for 1 h at 75% of their mode-specific VO2max or rested (S) and consumed water (SW, CYW, RW) or a 7% carbohydrate solution (SC, CYC, RC) at a rate of 10 ml.kg-1.h-1 (approximately 180 ml at 0, 15, 30, and 45 min). No differences were found between CYW, CYC, RW, RC, and SC for volume of drink emptied (mean +/- SE) (522.8 +/- 47.9 ml) and GE rate (range, 8.2 +/- 0.9 (RC) to 9.3 +/- 0.6 ml.min-1 (SC]. A mean of 72.7 +/- 5.7% of the total consumed volume was emptied. The GE rate during SW was significantly (P less than 0.05) greater than the other conditions (11.3 +/- 0.4 ml.min-1, 94.0 +/- 1.9% of total consumed volume emptied). Substantial volumes of water and a 7% carbohydrate solution are thus emptied from the stomach during prolonged, intense running and cycling, with no differences in GE between these exercise modes. These data suggest that recommendations concerning GE are reciprocal between running and cycling bouts similar to those in the current study.

This study examined the effects of a short-term sudden increment in training load on the oxidative capacity, glycogen content and tension-generating ability of rat skeletal muscle. After training on a treadmill 5 dwk-1 for 9 wk (30 m.min-1 6 degrees, 60 min.d-1), rats were randomly divided into a normal training volume (NTV) group (N = 11) and an increased training volume (ITV) group (N = 8). The NTV group were sacrificed 24 h after the last bout of exercise, while the ITV group continued to train for further 6 successive days. Training duration for this latter group was increased to 120 min.d-1 for the first 2 d; 240 min.d-1 for the next 2 d; and 360 min.d-1 for the final 2 d; speed and grade were kept constant. Respiratory capacity (QO2) and citrate synthase activity were increased (P less than 0.05) in both the soleus and plantaris muscles, with no change in the white vastus lateralis muscle of the NTV group when compared to age- matched sedentary controls. Glycogen levels were unchanged in these muscles, but liver glycogen content was greater (231.9 +/- 10.1 vs 156.8 +/- 15.3 umol.g-1 w.w. for the NTV vs age-matched sedentary controls, respectively, P less than 0.05). Peak tetanic tension in the gastrocnemius was not changed by training, or the increased training load. Citrate synthase activity (umol.min-1.g-1) was significantly greater (P less than 0.05) in the plantaris (33.3 +/- 1.0 vs 27.0 +/- 1.7) and soleus muscles (40.5 +/- 2.7 vs 28.4 +/- 1.3) in the ITV vs NTV groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to compare gastric emptying (GE) responses during intense, prolonged cycling and running. It is important to discern whether gastric emptying (GE) responses are exercise-mode specific, since the findings of cycling and running studies are often compared and applied to one another. Ten male biathletes cycled (CY) and ran (R) for 1 h at 75% of their mode-specific VO2max or rested (S) and consumed water (SW, CYW, RW) or a 7% carbohydrate solution (SC, CYC, RC) at a rate of 10 ml.kg-1.h-1 (approximately 180 ml at 0, 15, 30, and 45 min). No differences were found between CYW, CYC, RW, RC, and SC for volume of drink emptied (mean +/- SE) (522.8 +/- 47.9 ml) and GE rate (range, 8.2 +/- 0.9 (RC) to 9.3 +/- 0.6 ml.min-1 (SC]. A mean of 72.7 +/- 5.7% of the total consumed volume was emptied. The GE rate during SW was significantly (P less than 0.05) greater than the other conditions (11.3 +/- 0.4 ml.min-1, 94.0 +/- 1.9% of total consumed volume emptied). Substantial volumes of water and a 7% carbohydrate solution are thus emptied from the stomach during prolonged, intense running and cycling, with no differences in GE between these exercise modes. These data suggest that recommendations concerning GE are reciprocal between running and cycling bouts similar to those in the current study.

To examine the physiological responses to successive days of intense training, 12 male collegiate swimmers doubled their training distance (4,266 +/- 264 to 8,970 +/- 161 m.d-1) while maintaining the intensity at approximately 95% VO2max for 10 d. Blood samples were obtained pre-exercise and immediately and 5 min after a sub-maximal (approximately 95% VO2max) front crawl swim (365.8 m) on days 0, 5, and 11. Swim performance was assessed from a maximal front crawl swim (365.8 m), two maximal front crawl sprints (22.9 m), and a semi-tethered swim power test. No significant changes were observed in performance. Pre-exercise serum cortisol (17.5 +/- 1.5, 19.5 +/- 1.6, and 20.6 +/- 1.2 micrograms.dl-1 for days 0, 5, and 11, respectively) and creatine kinase (56.2 +/- 7.7, 93.1 +/- 10.1, and 119.0 +/- 23.1 U.l-1 for days 0, 5, and 11, respectively) values were significantly elevated (P less than 0.05) on days 5 and 11 compared to day 0. Resting plasma catecholamine concentrations were higher but not significantly different (P greater than 0.05) at the end of the training period. Measurements of hemoglobin and hematocrit indicated a relative increase of 11.4 +/- 2.7% (P less than 0.05) in estimated plasma volume during the training period. Resting blood glucose values were unaffected by the training regimen while small but significant decreases in resting blood lactate values (1.01 +/- 0.06, 0.85 +/- 0.06, and 0.86 +/- 0.06 mmol.l-1 for days 0, 5, and 11, respectively) were observed on days 5 and 11. Resting heart rate and systolic blood pressure were not affected by the increased training load.(ABSTRACT TRUNCATED AT 250 WORDS)

This investigation studied the importance of muscle glycogen levels for body temperature regulation during cold stress. Physiological responses of eight euglycemic males were measured while they rested in cold (18 degrees C, stirred) water on two separate occasions. The trials followed a 3-day program of diet and exercise manipulation designed to produce either high (HMG) or low (LMG) preimmersion glycogen levels in the muscles of the legs, arms, and upper torso. Preimmersion vastus lateralis muscle glycogen concentrations were lower during the LMG trial (144 +/- 14 mmol glucose/kg dry tissue) than the HMG trial (543 +/- 53 mmol glucose/kg dry tissue). There were no significant differences between the two trials in shivering as reflected by aerobic metabolic rate or in the amount of body cooling as reflected by changes in rectal temperature during the immersions. Postimmersion muscle glycogen levels remained unchanged from preimmersion levels in both trials. Small but significant increases in plasma glucose and lactate concentration occurred during both immersions. Plasma glycerol increased during immersion in the LMG trial but not in the HMG trial. Plasma free fatty acid concentration increased during both immersion trials, but the change was apparent sooner in the LMG immersion. It was concluded that thermoregulatory responses of moderately lean and fatter individuals exposed to cold stress were not impaired by a substantial reduction in the muscle glycogen levels of several major skeletal muscle groups. Furthermore, the data suggest that, depending on the intensity of shivering, other metabolic substrates are available to enable muscle glycogen to be spared.

In an effort to determine the effects of carbohydrate (CHO) feedings immediately before exercise in both the fasted and fed state, 10 well-trained male cyclists [maximum O2 consumption (VO2 max), 4.35 +/- 0.11 l/min)] performed 45 min of cycling at 77% VO2 max followed by a 15-min performance ride on an isokinetic cycle ergometer. After a 12-h fast, subjects ingested 45 g of liquid carbohydrate (LCHO), solid carbohydrate confectionery bar (SCHO), or placebo (P) 5 min before exercise. An additional trial was performed in which a high-CHO meal (200 g) taken 4 h before exercise was combined with a confectionery bar feeding (M + SCHO) immediately before the activity. At 10 min of exercise, serum glucose values were elevated by 18 and 24% during SCHO and LCHO, respectively, compared with P. At 0 and 45 min no significant differences were observed in muscle glycogen concentration or total use between the four trials. Total work produced during the final 15 min of exercise was significantly greater (P less than 0.05) during M + SCHO (194,735 +/- 9,448 N X m), compared with all other trials and significantly greater (P less than 0.05) during LCHO and SCHO (175,204 +/- 11,780 and 176,013 +/- 10,465 N X m, respectively) than trial P (159,143 +/- 11,407 N X m). These results suggest that, under conditions when CHO stores are less than optimal, exercise performance is enhanced with the ingestion of 45 g of CHO 5 min before 1 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the effects of acute heat stress, heat acclimation and hypohydration on the gastric emptying rate of water (W) during treadmill exercise, ten physically fit men ingested 400 ml of W before each of three 15 min bouts of exercise (treadmill, ∼50% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ ) on five seperate occasions. Stomach contents were aspirated after each exercise bout. Before heat acclimation (ACC), experiments were performed in a neutral (18°C), hot (49°C) and warm (35°C) environment. Subjects were euhydrated for all experiments before ACC. After ACC, the subjects completed two more experiments in the warm (35°C) environment; one while euhydrated and a final one while hypohydrated (-5% of body weight). The volume of ingested water emptied into the intestines at the completion of each exercise bout was inversely correlated (P

Eight well-trained male cyclists were used to determine the influence of carbohydrate feedings on exercise performance and muscle glycogen use. Two days prior to each trial, the subjects performed a 60-min "depletion ride" at 70% VO2max, which was followed by the ingestion of a high carbohydrate diet (approximately 500 g X -1). During the experimental trials, the men performed 2 h of cycling exercise and consumed 150 ml of 1 of 4 solutions at 24-min intervals. The drinks were: H2O (artificially flavored and sweetened); maltodextrin (5 g X 100 ml-1) and fructose (5 g X 100 ml-1); maltodextrin (7.7 g X 100 ml-1) and high fructose corn syrup (2.3 g X 100 ml-1); maltodextrin (3 g X 100 ml-1 and glucose (2 g X 100 ml-1). The amount of work completed during the four trials was not significantly different. Initial glycogen levels were high, and glycogen values were not significantly different at the beginning of exercise or at 90 min (185.35 +/- 3.26 and 91.93 +/- 3.39, respectively). Blood glucose was greater at 60 min in trial maltodextrin and glucose (5.70 +/- 0.36 mmoles X l-1), maltodextrin and high fructose corn syrup (6.05 +/- 0.54), and maltodextrin and fructose (6.03 +/- 0.42) compared to H2O (4.97 +/- 0.35) (P less than 0.05). Blood glucose remained elevated at 90 min during the maltodextrin and fructose and maltodextrin and high fructose corn syrup trials and at 120 min in the maltodextrin and fructose trial. No differences were observed between trials in blood lactate, serum glycerol, respiratory exchange ratio, or the subjects' perception of effort.(ABSTRACT TRUNCATED AT 250 WORDS)

Following 5 months of competitive training (approximately 9,000 yards.d-1, 6 d.wk-1), three groups of eight male swimmers performed 4 wk of either reduced training (3,000 yard.session-1) or inactivity. Two groups reduced their training to either 3 sessions.wk-1 (RT3) or 1 session.wk-1 (RT1), whereas the third group (IA) did no training. Measurement of muscular strength (biokinetic swim bench) showed no decrement in any group over the 4 wk. In contrast, swim power (tethered swim) was significantly decreased (P less than 0.05) in all groups, reaching a mean change of -13.6% by week 4. Blood lactate measured after a standard 200-yard (183 m) front crawl swim increased by 1.8, 3.5, and 5.5 mM over the 4 wk in groups RT3, RT1 and IA, respectively. In group RT1, stroke rate measured during the 200-yard swim significantly increased (P less than 0.05) from 0.54 +/- 0.03 to 0.59 +/- 0.03 strokes.-1 while stroke distance significantly decreased (P less than 0.05) from 2.50 +/- 0.08 to 2.29 +/- 0.13 m.stroke-1 during the 4-wk period. Both stroke rate and stroke distance were maintained in group RT3 over the 4 wk of reduced training. Group IA was not tested for stroke mechanics. Whereas maximal oxygen uptake decreases significantly (P less than 0.05) over the 4 wk in group RT1 (4.75 to 4.62 l.min-1), no change in maximal oxygen uptake was observed in group RT3. These results suggest that aerobic capacity is maintained over 4 wk of moderately reduced training (3 sessions.wk-1) in well-trained swimmers. Muscular strength was not diminished over 4 wk of reduced training or inactivity, but the ability to generate power during swimming was significantly reduced in all groups.

To examine the gastric emptying characteristics of selected test drinks varying in carbohydrate composition and concentration, twenty-five runners ingested 400 ml of a solution in one or more of a series of trials followed by either 15 min seated rest or 15 min running (50 to 70% VO2 max). The solutions tested at rest included water, 5.0% maltodextrin, 3.0% maltodextrin + 2% glucose (MG5.0), and 4.5% maltodextrin + 2.6% fructose (MF7.1). Solutions tested during running included water, MG5.0, MF7.1, 5.5% maltodextrin + 2% glucose, and 5.5% maltodextrin + 2% fructose. At rest and during running, water emptied significantly (P less than 0.5) faster than all other drinks. In the running trials, the volume of gastric residue of 5.5% maltodextrin + 2% fructose (221.7 +/- 11.0 ml) was significantly greater than water (103.4 +/- 19.0 ml), MG5.0 (153.3 +/- 16.8 ml), and MF7.1 (167.3 +/- 14.8), suggesting an inhibitory role of glucose on gastric emptying. Running resulted in a significantly lower volume of gastric residue of water, MG5.0, and MF7.1 (103.4 +/- 19.0, 153.3 +/- 16.8, and 167.3 +/- 14.8 ml, respectively) as compared to the corresponding drinks at rest (209.3 +/- 12.6, 287.7 +/- 16.0, and 271.0 +/- 17.8 ml, respectively). These results suggest a possible advantage for including maltodextrin and fructose as carbohydrate sources in athletic drinks. Furthermore, the rate of gastric emptying is enhanced while running, possibly due to increased mechanical movement of fluid within the stomach.

Gastric emptying is increased during running (50%–70% maximal aerobic uptake, $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ as compared to rest. Whether this increase varies as a function of mode (i. e. walking vs running) and intensity of treadmill exercise is unknown. To examine the gastric emptying characteristics of water during treadmill exercise performed over a wide range of intensities relative to resting conditions, 10 men ingested 400 ml of water prior to each of six 15 min exercise bouts or 15 min of seated rest. Three bouts of walking exercise (1.57 m · s−1) were performed at increasing grades eliciting ∼28%, 41% or 56% of $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ . On a seperate day, three bouts of running (2.68 ms−1) exercise were performed at grades eliciting ∼57%, 65% or 75% of $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ . Gastric emptying was increased during treadmill exercise at all intensities excluding 75% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ as compared to rest. Gastric emptying was similar for all intensities during walking and at 57% and 65% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ during running. However, running at 74% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ decreased the volume of original drink emptied as compared to all lower exercise intensities. Stomach secretions were markedly less during running as compared to walking and rest. These data demonstrate that gastric emptying is similarly increased during both moderate intensity (∼8%–65% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ ) walking or running exercise as compared to resting conditions. However, gastric emptying decreases during high intensity exercise. Increases in gastric emptying during moderate intensity treadmill exercise may be related to increases in intragastric pressure brought about by contractile activity of the abdominal muscles.

To examine the influence of muscle glycogen on the thermal responses to passive rewarming subsequent to mild hypothermia, eight subjects completed two cold-water immersions (18 degrees C), followed by 75 min of passive rewarming (24 degrees C air, resting in blanket). The experiments followed several days of different exercise-diet regimens eliciting either low (LMG; 141.0 +/- 10.5 mmol.kg.dry wt-1) or normal (NMG; 526.2 +/- 44.2 mmol.kg.dry wt-1) prewarming muscle glycogen levels. Cold-water immersion was performed for 180 min or to a rectal temperature (Tre) of 35.5 degrees C. In four subjects (group A, body fat = 20 +/- 1%), postimmersion Tre was similar to preimmersion Tre for both trials (36.73 +/- 0.18 vs. 37.26 +/- 0.18 degrees C, respectively). Passive rewarming in group A resulted in an increase in Tre of only 0.13 +/- 0.08 degrees C. Conversely, initial rewarming Tre for the other four subjects (group B, body fat = 12 +/- 1%) averaged 35.50 +/- 0.05 degrees C for both trials. Rewarming increased Tre similarly in group B during both LMG (0.76 +/- 0.25 degrees C) and NMG (0.89 +/- 0.13 degrees C). Afterdrop responses, evident only in those individuals whose body core cooled during immersion (group B), were not different between LMG and NMG. These data support the contention that Tre responses during passive rewarming are related to body insulation. Furthermore these results indicate that low muscle glycogen levels do not impair rewarming time nor alter after-drop responses during passive rewarming after mild-to-moderate hypothermia.

Following 5 months of competitive training (approximately 9,000 yards.d-1, 6 d.wk-1), three groups of eight male swimmers performed 4 wk of either reduced training (3,000 yard.session-1) or inactivity. Two groups reduced their training to either 3 sessions.wk-1 (RT3) or 1 session.wk-1 (RT1), whereas the third group (IA) did no training. Measurement of muscular strength (biokinetic swim bench) showed no decrement in any group over the 4 wk. In contrast, swim power (tethered swim) was significantly decreased (P less than 0.05) in all groups, reaching a mean change of -13.6% by week 4. Blood lactate measured after a standard 200-yard (183 m) front crawl swim increased by 1.8, 3.5, and 5.5 mM over the 4 wk in groups RT3, RT1 and IA, respectively. In group RT1, stroke rate measured during the 200-yard swim significantly increased (P less than 0.05) from 0.54 +/- 0.03 to 0.59 +/- 0.03 strokes.-1 while stroke distance significantly decreased (P less than 0.05) from 2.50 +/- 0.08 to 2.29 +/- 0.13 m.stroke-1 during the 4-wk period. Both stroke rate and stroke distance were maintained in group RT3 over the 4 wk of reduced training. Group IA was not tested for stroke mechanics. Whereas maximal oxygen uptake decreases significantly (P less than 0.05) over the 4 wk in group RT1 (4.75 to 4.62 l.min-1), no change in maximal oxygen uptake was observed in group RT3. These results suggest that aerobic capacity is maintained over 4 wk of moderately reduced training (3 sessions.wk-1) in well-trained swimmers. Muscular strength was not diminished over 4 wk of reduced training or inactivity, but the ability to generate power during swimming was significantly reduced in all groups.

To examine the gastric emptying characteristics of selected test drinks varying in carbohydrate composition and concentration, twenty-five runners ingested 400 ml of a solution in one or more of a series of trials followed by either 15 min seated rest or 15 min running (50 to 70% VO2 max). The solutions tested at rest included water, 5.0% maltodextrin, 3.0% maltodextrin + 2% glucose (MG5.0), and 4.5% maltodextrin + 2.6% fructose (MF7.1). Solutions tested during running included water, MG5.0, MF7.1, 5.5% maltodextrin + 2% glucose, and 5.5% maltodextrin + 2% fructose. At rest and during running, water emptied significantly (P less than 0.5) faster than all other drinks. In the running trials, the volume of gastric residue of 5.5% maltodextrin + 2% fructose (221.7 +/- 11.0 ml) was significantly greater than water (103.4 +/- 19.0 ml), MG5.0 (153.3 +/- 16.8 ml), and MF7.1 (167.3 +/- 14.8), suggesting an inhibitory role of glucose on gastric emptying. Running resulted in a significantly lower volume of gastric residue of water, MG5.0, and MF7.1 (103.4 +/- 19.0, 153.3 +/- 16.8, and 167.3 +/- 14.8 ml, respectively) as compared to the corresponding drinks at rest (209.3 +/- 12.6, 287.7 +/- 16.0, and 271.0 +/- 17.8 ml, respectively). These results suggest a possible advantage for including maltodextrin and fructose as carbohydrate sources in athletic drinks. Furthermore, the rate of gastric emptying is enhanced while running, possibly due to increased mechanical movement of fluid within the stomach.

Eight well-trained male cyclists were used to determine the influence of carbohydrate feedings on exercise performance and muscle glycogen use. Two days prior to each trial, the subjects performed a 60-min "depletion ride" at 70% VO2max, which was followed by the ingestion of a high carbohydrate diet (approximately 500 g X -1). During the experimental trials, the men performed 2 h of cycling exercise and consumed 150 ml of 1 of 4 solutions at 24-min intervals. The drinks were: H2O (artificially flavored and sweetened); maltodextrin (5 g X 100 ml-1) and fructose (5 g X 100 ml-1); maltodextrin (7.7 g X 100 ml-1) and high fructose corn syrup (2.3 g X 100 ml-1); maltodextrin (3 g X 100 ml-1 and glucose (2 g X 100 ml-1). The amount of work completed during the four trials was not significantly different. Initial glycogen levels were high, and glycogen values were not significantly different at the beginning of exercise or at 90 min (185.35 +/- 3.26 and 91.93 +/- 3.39, respectively). Blood glucose was greater at 60 min in trial maltodextrin and glucose (5.70 +/- 0.36 mmoles X l-1), maltodextrin and high fructose corn syrup (6.05 +/- 0.54), and maltodextrin and fructose (6.03 +/- 0.42) compared to H2O (4.97 +/- 0.35) (P less than 0.05). Blood glucose remained elevated at 90 min during the maltodextrin and fructose and maltodextrin and high fructose corn syrup trials and at 120 min in the maltodextrin and fructose trial. No differences were observed between trials in blood lactate, serum glycerol, respiratory exchange ratio, or the subjects' perception of effort.(ABSTRACT TRUNCATED AT 250 WORDS)