Biomedical subjects

G J Heigenhauser

Publications and source records attributed to G J Heigenhauser.

At least 19 recordsLinked to original sources

PubMed2001

Creatine supplementation affects sprint endurance in juvenile rainbow trout.

Fingerling rainbow trout were supplemented with equal amounts of creatine (Cr) by two routes: dietary (12.5 mg Cr per g food); or intraperitoneal injection (0.5 mg Cr per g fish). Endurance in a fixed velocity sprint test (at a speed of 7 BL s(-1)), and resting levels of white muscle metabolites (total creatine [a measure of free creatine plus phosphocreatine (PCr), ATP, lactate and glycogen] were assessed following 7 days of supplementation and compared to controls. None of the treatments had a significant effect on growth, muscle total creatine, percent phosphorylation of creatine, ATP or lactate. However, resting muscle glycogen was elevated in creatine-supplemented fish. Higher muscle glycogen corresponded to significantly greater endurance in creatine-supplemented fish. Although fish do not actively transport additional creatine into the muscle, a mechanism whereby circulating creatine acts to enhance muscle glycogen is present. These results suggest that the improved endurance may be due to an insulin-dependent mechanism (similar to that elucidated in mammalian studies) that allows fish to supercompensate muscle glycogen stores, thus extending endurance through enhanced glycolytic flux.

Adenosine Triphosphate↗

PubMed2001

Effects of acetate infusion and hyperoxia on muscle substrate phosphorylation after onset of moderate exercise.

This study investigated whether increased muscle acetylcarnitine provision (acetate infusion) or hyperoxia (100% O(2)) would increase the rate of oxidative phosphorylation and reduce the reliance on muscle substrate phosphorylation after the onset of moderate exercise. Eight subjects completed three randomized trials, each separated by 1 wk: 1) saline infusion for 1 h before exercise, while breathing room air for 20 min before exercise and during 120 s of cycling at 65% maximal exercise (VO(2 max)) (CON), 2) saline infusion with 4 mmol/kg body wt sodium acetate, while breathing room air before and during exercise (ACE), and 3) saline infusion and breathing 100% O(2) before and during exercise (HYP). Muscle biopsies were sampled at rest and after 30 and 120 s of exercise. ACE increased muscle acetyl-CoA and acetylcarnitine contents at rest vs. CON and HYP [22.9 +/- 2.8 vs. 8.9 +/- 2.4 and 10.5 +/- 1.8 micromol/kg dry muscle (dm); 11.0 +/- 1.2 vs. 3.5 +/- 1.3 and 4.0 +/- 1.2 mmol/kg dm]. Acetate had no effect on resting pyruvate dehydrogenase activity in the active form (PDH(a)) among CON, ACE, and HYP. During exercise, acetyl-CoA and acetylcarnitine were unchanged in ACE but increased over time in the CON and HYP trials, and PDH(a) increased similarly in all trials. Muscle phosphocreatine use, lactate accumulation, and substrate phosphorylation energy provision after 30 or 120 s of exercise were similar in all trials. In summary, increased acetylcarnitine availability did not accelerate the rate of oxidative phosphorylation at the onset of exercise, suggesting that this is not a site of extra substrate. Hyperoxia had no effect on substrate phosphorylation, suggesting that O(2) availability does not limit oxidative phosphorylation at the onset of moderate exercise.

Acetates↗

PubMed2001

Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet.

The increase in skeletal muscle pyruvate dehydrogenase kinase (PDK) activity was measured in skeletal muscle of six healthy males after a eucaloric high-fat/low-carbohydrate (HF/LC; 5% carbohydrate, 73% fat, and 22% protein of total energy intake) diet compared with a standardized prediet (50% carbohdyrate, 30% fat, and 21% protein). Biopsies were obtained from the vastus lateralis muscle after 3 days on the prediet (day 0) and after 1, 2, and 3 days of the HF/LC diet. Intact mitchondria were extracted from fresh muscle and analyzed for PDK activity and Western blotting of PDK2 and PDK4 protein. A second biopsy was taken at each time point and frozen for Northern blot analysis of PDK2 and PDK4 mRNAs. PDK activity increased in a linear fashion over the 3-day HF/LC diet and was significantly higher than control by 1 day. PDK activity was 0.09 +/- 0.03, 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.37 +/- 0.09 min(-1) at 0, 1, 2, and 3 days, respectively. PDK4 protein and mRNA increased maximally by day 1, and PDK2 protein and mRNA were unaffected by the HF/LC diet. Resting respiratory exchange ratios decreased after 1 day of the HF/LC diet (from 0.79 +/- 0.02 to 0.72 +/- 0.02) and remained depressed throughout the 3-day dietary intervention (0.68 +/- 0.01). The immediate shift to fat utilization was accompanied by increased blood glycerol, beta-hydroxybutyrate, and plasma free fatty acid concentrations. These results suggest that the continuing increase in PDK activity over the 3-day HF/LC diet is not due to increasing PDK protein beyond 1 day. This could be due to the contribution of another isoform to the total PDK activity or to a continual increase in PDK4 or PDK2 specific activity.

Adult↗

PubMed2001

Muscle fiber type comparison of PDH kinase activity and isoform expression in fed and fasted rats.

Fiber type specificity for expression of all three rat skeletal muscle pyruvate dehydrogenase kinase (PDK) isoforms (PDK1, 2, and 4) was determined in fed and 24-h fasted rats. PDK activity and isoform protein and mRNA contents were determined in white gastrocnemius (WG; fast-twitch glycolytic), red gastrocnemius (RG; fast-twitch oxidative), and soleus (Sol; slow-twitch oxidative) muscles. PDK activity was lower in WG compared with oxidative muscles (RG, Sol) in both fed and fasted rats. PDK activities from fed muscles were 0.12 +/- 0.04, 0.30 +/- 0.01, and 0.36 +/- 0.08 min(-1) in WG, Sol, and RG, respectively, and increased in fasted muscles (0.36 +/- 0.09, 0.68 +/- 0.18, and 0.80 +/- 0.14 min(-1)). This correlated with increased PDK4 protein and to a lesser extent with PDK4 mRNA. PDK2 protein was not different between fiber types in fed or fasted rats, but PDK2 mRNA content was twofold greater in RG from fasted rats compared with fed rats. PDK1 was unaltered by fasting in all muscle types at both the protein and mRNA level, but in both fed and fasted rats had much greater protein and mRNA content in the oxidative vs. glycolytic muscles. In conclusion, PDK activity and PDK1 and 4 protein and mRNA were lower in glycolytic vs. oxidative muscles from fed and fasted rats. Fasting for 24 h induced a two- to threefold increase in PDK activity that was mainly due to increases in PDK4 protein and mRNA. PDK1 and 2 protein and mRNA were generally unaltered by fasting in all fiber types, except for increased PDK2 mRNA in the fast oxidative fibers. Because the PDK isoforms vary greatly in their kinetic properties, their relative proportions in the three fiber types at any given time during fasting could significantly alter the acute regulation of the pyruvate dehydrogenase complex.

Animals↗

PubMed2001

Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10--14 yr.

We measured substrate utilization during exercise performed with water (W), exogenous glucose (G), and exogenous fructose plus glucose (FG) ingestion in boys age 10-14 yr. Subjects (n = 12) cycled for 90 min at 55% maximal O(2) uptake while ingesting either W (25 ml/kg), 6% G (1.5 g/kg), or 3% F plus 3% G (1.5 g/kg). Fat oxidation increased during exercise in all trials but was higher in the W (0.28 +/- 0.023 g/min) than in the G (0.24 +/- 0.023 g/min) and FG (0.25 +/- 0.029 g/min) trials (P = 0.04). Conversely, total carbohydrate (CHO) oxidation decreased in all trials and was lower in the W (0.63 +/- 0.05 g/min) than in the G (0.78 +/- 0.051 g/min) and FG (0.74 +/- 0.056 g/min) trials (P = 0.009). Exogenous CHO oxidation, as determined by expired (13)CO(2), reached a maximum of 0.36 +/- 0.032 and 0.31 +/- 0.030 g/min at 90 min in G and FG, respectively (P = 0.04). Plasma insulin levels decrease during exercise in all trials but were twofold higher in G than in W and FG (P < 0.001). Plasma glucose levels decreased transiently after the onset of exercise in all trials and then returned to preexercise values in the W and FG (approximately 4.5 mmol/l) trials but were elevated by approximately 1.0 mmol/l in the G trial (P < 0.001). Plasma lactate concentrations decreased after the onset of exercise in all trials but were lower by approximately 0.5 mmol/l in W than in G and FG (P = 0.02). Thus, in boys exercising at a moderate intensity, the oxidation rate of G plus F is slightly less than G alone, but both spare endogenous CHO and fat to a similar extent. In addition, compared with flavored W, the ingestion of G alone and of G plus F delays exhaustion at 90% peak power by approximately 25 and 40%, respectively, after 90 min of moderate-intensity exercise.

Adolescent↗

PubMed2000

Substrate utilization in boys during exercise with [13C]-glucose ingestion.

The influence of glucose ingestion on substrate utilization during prolonged exercise in children and adolescents is currently unknown. In the present study we determined the effect of intermittent exogenous glucose (GLUexo) ingestion on substrate utilization during prolonged exercise, in adolescent boys ages 13 17 years. Healthy untrained volunteers performed four 30-min exercise bouts on a cycle ergometer, separated by 5-min rest periods (approximately equal to 60% maximum O2 consumption), on two occasions spaced 1-4 weeks apart. Two trials were performed, a control trial (CT), in which subjects ingested water intermittently during the exercise, and a glucose trial (GT), in which subjects ingested a 13C-enriched GLUexo drink (approximately egual to glucose kg body mass(-1)), also intermittently during the exercise. Total free fatty acids (FATtotal), glucose (GLUtotal) and carbohydrate (CHOtotal) oxidation was determined from indirect calorimetry, while GLUexo oxidation was calculated from the 13C/12C ratio in expired air after 5-10 min and 25-30 min of exercise in each bout. Heart rate and rating of perceived exertion (RPE) were determined at the same time intervals. The oxidation of CHOtotal was 169.1 (12.9) g x 120 min(-1) and 203.1 (15.9) g x 120 min(-1) (P < 0.01) and that of FATtotal was 31.0 (4.2) g x 120 min(-1) and 17.1 (2.5) g x 120 min(-1) (P < 0.01) in CT and GT, respectively. GLUexo oxidation in GT was 57.8 (4.3) g x 120 min(-1), or 34.2 (2.2)% of that ingested. Endogenous glucose oxidation was 169.1 (12.9) g x 120 min(-1) and 145.3 (11.9) g x 120 min(-1) (P < 0.01) in CT and GT, respectively. Insulin and glucose concentrations were higher in GT than in CT by 226% and 37%, respectively (both P < 0.05). Free fatty acids and glycerol concentrations were lower in GT than in CT, by 27% and 79%, respectively (both P < 0.05). Heart rate was similar between trials, but RPE was lower in GT vs CT at both 115 and 135 min. Thus, under these experimental conditions, GLUexo intake spares endogenous carbohydrate and fat by 16% and 45%, respectively, contributes to approximately 25% of the total energy demand of exercise, and lowers the RPE.

Adolescent↗

PubMed2000

Perceived exertion with glucose ingestion in adolescent males with IDDM.

PURPOSE: The rating of perceived exertion (RPE) is an indicator of exercise effort in adolescents that may be influenced by certain pediatric conditions. The purpose of this study was to determine the influence of insulin-dependent diabetes mellitus (IDDM) and glucose intake on RPE. METHODS: Eight male adolescents with IDDM and eight healthy controls of similar age, weight, and VO2peak cycled for 60 min at 60%VO2peak on two occasions spaced 1-4 wk apart. During a control trial (CT), subjects drank water, and in a glucose trial (GT), glucose at a rate of approximately 1.5 g x kg(-1) x h(-1). Heart rate, ventilation, and RPE (Borg 6-20 scale) were assessed at 5, 25, 35, and 55 min and blood glucose and lactate levels before and at 30 and 60 min. RESULTS: RPE in both trials was 15-25% higher in IDDM versus healthy subjects (F = 8.83; df = 1,14; eta-squared = 0.39; P = 0.01). In CT, it increased from 10.6 +/- 0.4 at 5 min to 15.2 +/- 0.6 at 55 min in IDDM and from 9.3 +/- 0.9 at 5 min to 13.0 +/- 0.8 at 55 min in healthy adolescents. In GT, RPE increased similarly to CT in the IDDM group but was 1-2 points lower in the healthy group. Blood glucose levels were 4.8 +/- 1.8 mmol x L(-1) and 1.8 +/- 0.4 mmol x L(-1) higher by the end of exercise in GT than in CT for the IDDM and healthy groups, respectively. There were no differences in heart rate, ventilation, or lactate levels between the groups or trials. CONCLUSIONS: For exercise performed at a similar moderate intensity, RPE in IDDM is higher by 2-3 points than in controls. Compared with water, glucose intake is associated with lower RPE in healthy, but not in IDDM, adolescents.

Adolescent↗

PubMed2000

An enzymatic approach to lactate production in human skeletal muscle during exercise.

PURPOSE: This paper examines the production of lactate in human skeletal muscle over a range of power outputs (35-250% VO2max) from an enzymatic flux point of view. The conversion of pyruvate and NADH to lactate and NAD in the cytoplasm of muscle cells is catalyzed by the near-equilibrium enzyme lactate dehydrogenase (LDH). As flux through LDH is increased by its substrates, pyruvate and NADH, the factors governing the production of these substrates will largely dictate how much lactate is produced at any exercise power output. In an attempt to understand lactate production, flux rates through the enzymes that regulate glycogenolysis/glycolysis, the transfer of cytoplasmic reducing equivalents into the mitochondria, and the various fates of pyruvate have been measured or estimated. RESULTS: At low power outputs, the rates of pyruvate and NADH production in the cytoplasm are low, and pyruvate dehydrogenase (PDH) and the shuttle system enzymes (SS) metabolize the majority of these substrates, resulting in little or no lactate production. At higher power outputs (65, 90, and 250% VO2max), the mismatch between the ATP demand and aerobic ATP provision at the onset of exercise increases as a function of intensity, resulting in increasing accumulations of the glycogenolytic/glycolytic activators (free ADP, AMP, and Pi). The resulting glycolytic flux, and NADH and pyruvate production, is progressively greater than can be handled by the SS and PDH, and lactate is produced at increasing rates. Lactate production during the onset of exercise and 10 min of sustained aerobic exercise may be a function of adjustments in the delivery of O2 to the muscles, adjustments in the activation of the aerobic ATP producing metabolic pathways and/or substantial glycogenolytic/glycolytic flux through a mass action effect.

Adenosine Triphosphate↗

PubMed2000

Effect of induced metabolic alkalosis on human skeletal muscle metabolism during exercise.

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDH(a)), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO(3) [metabolic alkalosis (ALK)] or CaCO(3) [control (CON)]. Subjects (n = 8) were studied at rest, rest postingestion, and during constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O(2) uptake (VO(2 max)). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly (P < 0.05) higher intramuscular Lac(-) concentration ([Lac(-)]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac(-)] (ALK 8.7 vs. CON 7.0 mmol/l), and leg Lac(-) efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% VO(2 max). The increased intramuscular [Lac(-)] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADP(f)), free AMP (AMP(f)), and free P(i) concentrations. PDH(a) increased with ALK at 60% VO(2 max) but was similar to CON at 75% VO(2 max). The increased PDH(a) may have resulted from alterations in the acetyl-CoA, ADP(f), pyruvate, NADH, and H(+) concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% VO(2 max) may have reflected maximal activation. The results demonstrate that imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidation resulting in an increase in Lac(-) production.

Adenine Nucleotides↗

PubMed2000

Sensitivity of CPT I to malonyl-CoA in trained and untrained human skeletal muscle.

The present study examined the sensitivity of carnitine palmitoyltransferase I (CPT I) activity to its inhibitor malonyl-CoA (M-CoA), and simulated metabolic conditions of rest and exercise, in aerobically trained and untrained humans. Maximal CPT I activity was measured in mitochondria isolated from resting human skeletal muscle. Mean CPT I activity was 492.8 +/- 72.8 and 260.8 +/- 33.6 micromol. min(-1). kg wet muscle(-1) in trained and untrained subjects, respectively (pH 7.0, 37 degrees C). The sensitivity to M-CoA was greater in trained muscle; the IC(50) for M-CoA was 0.17 +/- 0.04 and 0.49 +/- 0.17 microM in trained and untrained muscle, respectively. The presence of acetyl-CoA, free coenzyme A (CoASH), and acetylcarnitine, in concentrations simulating rest and exercise conditions did not release the M-CoA-induced inhibition of CPT I activity. However, CPT I activity was reduced at pH 6.8 vs. pH 7.0 in both trained and untrained muscle in the presence of physiological concentrations of M-CoA. The results of this study indicate that aerobic training is associated with an increase in the sensitivity of CPT I to M-CoA. Accumulations of acetyl-CoA, CoASH, and acetylcarnitine do not counteract the M-CoA-induced inhibition of CPT I activity. However, small decreases in pH produce large reductions in the activity of CPT I and may contribute to the decrease in fat metabolism that occurs during moderate and intense aerobic exercise intensities.

Acetyl Coenzyme A↗

PubMed2000

Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia.

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O(2) (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.

Adenosine Triphosphate↗

PubMed2000

Pyruvate overrides inhibition of PDH during exercise after a low-carbohydrate diet.

The effects of carbohydrate deprivation on the regulation of pyruvate dehydrogenase (PDH) were studied at rest and during moderate-intensity exercise. An inhibitory effect of a chronic low-carbohydrate diet (LCD) on the active form of PDH (PDHa) mediated by a stable increase in PDH kinase (PDHK) activity has recently been reported (Peters SJ, Howlett RA, St. Amand TA, Heigenhauser GJF, and Spriet LL. Am J Physiol Endocrinol Metab 275: E980-E986, 1998.). In the present study, seven males cycled at 65% maximal O(2) uptake for 30 min after a 6-day LCD. Exercise was repeated 1 wk later after a mixed diet (MD). Muscle biopsies were sampled from the vastus lateralis at rest and at 2 and 30 min of exercise. At rest, PDHa activity (0.18 +/- 0.04 vs. 0.63 +/- 0.18 mmol x min(-1) x kg wet wt(-1)), muscle glycogen content (310.2 +/- 36.9 vs. 563.9 +/- 32.6 mmol/kg dry wt), and muscle lactate content (2.6 +/- 0.3 vs. 4.2 +/- 0.6 mmol/kg dry wt) were significantly lower after the LCD. Resting muscle acetyl-CoA (10.8 +/- 1.9 vs. 7.4 +/- 0.8 micromol/kg dry wt) and acetylcarnitine (5.3 +/- 1.4 vs. 1.6 +/- 0.3 mmol/kg dry wt) contents were significantly elevated after the LCD. During exercise, PDHa, glycogenolytic rate (LCD 5.8 +/- 0.4 vs. MD 6.9 +/- 0.2 mmol x min(-1) x kg dry wt(-1)), and muscle concentrations of acetylcarnitine, pyruvate, and lactate increased to the same extent in both conditions. The results of the present study suggest that inhibition of resting PDH by elevated PDHK activity after a LCD may be overridden by the availability of muscle pyruvate during exercise.

3-Hydroxybutyric Acid↗

PubMed2000

Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia.

During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000). The present study investigated whether activation of PDH with dichloroacetate (DCA) before exercise would reduce lactate accumulation during exercise in acute hypoxia by increasing oxidative phosphorylation. Six subjects cycled on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake after a saline (control) or DCA infusion while breathing 11% O(2). Muscle biopsies of the vastus lateralis were taken at rest and after 1 and 15 min of exercise. DCA increased PDH activity at rest and at 1 min of exercise, resulting in increased acetyl-CoA concentration and acetylcarnitine concentration at rest and at 1 min. In the first minute of exercise, there was a trend toward a lower phosphocreatine (PCr) breakdown with DCA compared with control. Glycogenolysis was lower with DCA, resulting in reduced lactate concentration ([lactate]), despite similar phosphorylase a mole fractions and posttransformational regulators. During the subsequent 14 min of exercise, PDH activity was similar, whereas PCr breakdown and muscle [lactate] were reduced with DCA. Glycogenolysis was lower with DCA, despite similar mole fractions of phosphorylase a, and was due to reduced posttransformational regulators. The results from the present study support the hypothesis that lactate production is due in part to metabolic inertia and cannot solely be explained by an oxygen limitation, even under conditions of acute hypoxia.

Acetyl Coenzyme A↗

PubMed2000

NaHCO(3) and KHCO(3) ingestion rapidly increases renal electrolyte excretion in humans.

This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO(3) and KHCO(3) ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO(3)) and, in a separate trial, potassium bicarbonate (KHCO(3)). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO(3) ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 +/- 11% of ingested volume, resulting in a 555 +/- 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na(+) excretion accounted for 24 +/- 2% of ingested Na(+). In the KHCO(3) trial, arterial plasma K(+) concentration rapidly increased from 4.25 +/- 0.10 to a peak of 7.17 +/- 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K(+) excretion at 270 min accounted for 26 +/- 5% of ingested K(+). The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO(3) and NaHCO(3) solutions.

Acid-Base Equilibrium↗

PubMed2000

Glucose ingestion and substrate utilization during exercise in boys with IDDM.

This study was intended to compare exogenous [(13)C]glucose (Glu(exo)) oxidation in boys with insulin-dependent diabetes mellitus (IDDM) and healthy boys of similar age, weight, and maximal O(2) uptake. In a control trial with water intake (CT) and in a (13)C-enriched glucose trial (GT), subjects cycled for 60 min (58.8 +/- 0.9% maximal O(2) uptake) while the utilization of total glucose, total fat, and Glu(exo) was assessed. In CT, total glucose was 84.7 +/- 9.2 vs. 91.3 +/- 6.6 g/60 min (not significantly different) and total fat was 13.3 +/- 2.2 vs. 11.1 +/- 1.7 g/60 min (not significantly different) in IDDM vs. healthy boys, respectively. In GT, Glu(exo) was 10.4 +/- 1.7 vs. 14.8 +/- 1.1 g/60 min, corresponding to 9.0 +/- 1.0 vs. 12.4 +/- 0.5% of the total energy supply in IDDM and healthy boys, respectively (P < 0.05). Endogenous glucose was spared in both groups by 12.6 +/- 3.5% (P < 0.05). Blood glucose and plasma insulin concentrations were two- to threefold higher in IDDM vs. healthy boys in both trials. In conclusion, Glu(exo) is impaired in exercising boys with IDDM, even when plasma insulin levels are elevated.

Adolescent↗

PubMed2000

Dietary carbohydrate, muscle glycogen content, and endurance performance in well-trained women.

This study examined the ability of well-trained eumenorrheic women to increase muscle glycogen content and endurance performance in response to a high-carbohydrate diet (HCD; approximately 78% carbohydrate) compared with a moderate-carbohydrate diet (MD; approximately 48% carbohydrate) when tested during the luteal phase of the menstrual cycle. Six women cycled to exhaustion at approximately 80% maximal oxygen uptake (VO(2 max)) after each of the randomly assigned diet and exercise-tapering regimens. A biopsy was taken from the vastus lateralis before and after exercise in each trial. Preexercise muscle glycogen content was high after the MD (625.2 +/- 50.1 mmol/kg dry muscle) and 13% greater after the HCD (709.0 +/- 44.8 mmol/kg dry muscle). Postexercise muscle glycogen was low after both trials (MD, 91.4 +/- 34.5; HCD, 80.3 +/- 19.5 mmol/kg dry muscle), and net glycogen utilization during exercise was greater after the HCD. The subjects also cycled longer at approximately 80% VO(2 max) after the HCD vs. MD (115:31 +/- 10:47 vs. 106:35 +/- 8:36 min:s, respectively). In conclusion, aerobically trained women increased muscle glycogen content in response to a high-dietary carbohydrate intake during the luteal phase of the menstrual cycle, but the magnitude was smaller than previously observed in men. The increase in muscle glycogen, and possibly liver glycogen, after the HCD was associated with increased cycling performance to volitional exhaustion at approximately 80% VO(2 max).

Adult↗

PubMed2000

Effects of high fat provision on muscle PDH activation and malonyl-CoA content in moderate exercise.

This study examined the effects of elevated free fatty acid (FFA) provision on the regulation of pyruvate dehydrogenase (PDH) activity and malonyl-CoA (M-CoA) content in human skeletal muscle during moderate-intensity exercise. Seven men rested for 30 min and cycled for 10 min at 40% and 10 min at 65% of maximal O(2) uptake while being infused with either Intralipid and heparin (Int) or saline (control). Muscle biopsies were taken at 0, 1 (rest-to-exercise transition), 10, and 20 min. Exercise plasma FFA were elevated (0.99 +/- 0.11 vs. 0.33 +/- 0.03 mM), and the respiratory exchange ratio was reduced during Int (0.87 +/- 0.02) vs. control (0.91 +/- 0.01). PDH activation was lower during Int at 1 min (1.33 +/- 0.19 vs. 2.07 +/- 0.14 mmol. min(-1). kg(-1) wet muscle) and throughout exercise. Muscle pyruvate was reduced during Int at rest [0.17 +/- 0.03 vs. 0.25 +/- 0.03 mmol/kg dry muscle (dm)] but increased above control during exercise. NADH was higher during Int vs. control at rest and 1 min of exercise (0.122 +/- 0.016 vs. 0.102 +/- 0.005 and 0.182 +/- 0.016 vs. 0.150 +/- 0.016 mmol/kg dm), but not at 10 and 20 min. M-CoA was lower during Int vs. control at rest and 20 min of exercise (1.12 +/- 0.22 vs. 1.43 +/- 0.17 and 1.33 +/- 0.16 vs. 1.84 +/- 0.17 micromol/kg dm). The reduced PDH activation with elevated FFA during the rest-to-exercise transition was related to higher mitochondrial NADH at rest and 1 min of exercise and lower muscle pyruvate at rest. The decreased M-CoA may have increased fat oxidation during exercise with elevated FFA by reducing carnitine palmitoyltransferase I inhibition and increasing mitochondrial FFA transport.

Adult↗

PubMed1999

Role of pyruvate dehydrogenase in lactate production in exercising human skeletal muscle.

The mechanisms responsible for lactate production with increased intensity of muscle contraction are controversial. Some investigators suggest that the mitochondria are O2-limited, whereas others suggest that lactate production occurs when O2 to the mitochondria is adequate and that the increased lactate production is due to a "mass-action effect" when pyruvate production exceeds the rate of pyruvate oxidation. Pyruvate dehydrogenase is a rate-limiting enzyme for pyruvate entry into the tricarboxylic acid cycle; its catalytic activity influences both pyruvate oxidation and lactate production. Since lactate dehydrogenase is an equilibrium enzyme, increased lactate production will be due to a mass-action effect exerted by increases in pyruvate concentrations. Because the equilibrium constant of the lactate dehydrogenase reaction markedly favors lactate over pyruvate, small increases in pyruvate concentration will result in large increases in lactate concentration. At higher exercise intensities, which are more reliant on glycogen as substrate, the rate of pyruvate production exceeds the catalytic activity of pyruvate dehydrogenase, and lactate production occurs. Studies using dichloroacetate, induced acid-base changes, diet and short-term endurance training, indicate that lactate production is related to complex interactions of metabolic pathways and not related to inadequate O2 supply. As pyruvate dehydrogenase plays a central role in the integration of carbohydrate and fat metabolism, and in the entry of pyruvate into the tricarboxylic acid cycle, this enzyme plays a key role in lactate production.

Exercise↗