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1.
Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes.
Mackenzie, R, Maxwell, N, Castle, P, Elliott, B, Brickley, G, Watt, P
The Journal of clinical endocrinology and metabolism. 2012;(4):E546-55
Abstract
CONTEXT Hypoxia and muscle contraction stimulate glucose transport activity in vitro. Exercise and hypoxia have additive effects on insulin sensitivity in type 2 diabetics (T2D). OBJECTIVE The objective of the study was to examine the effectiveness of intermittent exercise with and without hypoxia on acute- and moderate-term glucose kinetics and insulin sensitivity in T2D. SETTING The study was conducted at a university research center. DESIGN, PARTICIPANTS, AND INTERVENTIONS Eight male T2D patients completed the following: 1) 60 min of continuous exercise at 90% lactate threshold in hypoxia (HyEx60); 2) intermittent exercise at 120% lactate threshold, separated by periods of passive recovery (5:5 min) in hypoxia [Hy5:5; O₂ ∼ 14.7 (0.2)%]; and 3) intermittent exercise (5:5 min) at 120% lactate threshold in normoxia (O₂ ∼ 20.93%). MAIN OUTCOME MEASURES Glucose appearance and glucose disappearance, using an adapted non-steady-state one-compartment model were measured. Homeostasis models of insulin resistance (HOMA(IR)), fasting insulin resistance index (FIRI), and β-cell function were calculated 24 and 48 h after exercise conditions. RESULTS Glucose disappearance increased from baseline (1.85 mg/kg · min⁻¹) compared with 24 h (2.01 min/kg · min⁻¹) after HyEx60 (P = 0.031). No difference was noted for both Hy5:5 (P = 0.064) and normoxia (P = 0.385). Hy5:5 demonstrated improvements in HOMA(IR) from baseline [d 1, 6.20 (0.40)] when comparisons were made with d 2 [4.83 (0.41)] (P = 0.0013). HOMA(IR) and FIRI improved in the 24 h (HOMA(IR), P = 0.002; FIRI, P = 0.003), remaining reduced 48 h after HyEx60 (HOMA(IR), P = 0.028; and FIRI, P = 0.034). CONCLUSION HyEx60 offered the greatest improvements in acute and moderate-term glucose control in T2D. Intermittent exercise stimulated glucose disposal and improved post-exercise insulin resistance, which was enhanced when exercise was combined with hypoxia (Hy5:5). The data suggest a use of hypoxic exercise in treatment of T2D.
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2.
Effect of weight loss on lactate transporter expression in skeletal muscle of obese subjects.
Metz, L, Mercier, J, Tremblay, A, Alméras, N, Joanisse, DR
Journal of applied physiology (Bethesda, Md. : 1985). 2008;(3):633-8
Abstract
The effects of weight loss on skeletal muscle lactate transporter [monocarboxylate transporter (MCT)] expression in obese subjects were investigated to better understand how lactate transporter metabolism is regulated in insulin-resistant states. Ten obese subjects underwent non-macronutrient-specific energy restriction for 15 wk. Anthropometric measurements and a needle biopsy of the vastus lateralis muscle before and after the weight loss program were performed. Enzymatic activity, fiber type distribution, and skeletal muscle MCT protein expression were measured. Muscle from nonobese control subjects was used for comparison of MCT levels. The program induced a weight loss of 9.2 +/- 1.6 kg. Compared with controls, muscle from obese subjects showed a strong tendency (P = 0.06) for elevated MCT4 expression (+69%) before the weight loss program. MCT4 expression decreased (-7%) following weight loss to reach levels that were not statistically different from control levels. There were no differences in MCT1 expression between controls and obese subjects before and after weight loss. A highly predictive regression model (R2 = 0.93), including waist circumference, citrate synthase activity, and percentage of type 1 fibers, was found to explain the highly variable MCT1 response to weight loss in the obese group. Therefore, in obesity, MCT1 expression appears linked both to changes in oxidative parameters and to changes in visceral adipose tissue content. The strong tendency for elevated expression of muscle MCT4 could reflect the need to release greater amounts of muscle lactate in the obese state, a situation that would be normalized with weight loss as indicated by decreased MCT4 levels.
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3.
Extracellular bicarbonate and non-bicarbonate buffering against lactic acid during and after exercise.
Böning, D, Klarholz, C, Himmelsbach, B, Hütler, M, Maassen, N
European journal of applied physiology. 2007;(4):457-67
Abstract
Defense of extracellular pH constancy against lactic acidosis can be estimated from changes (Delta) in lactic acid ([La]), [HCO(3)(-)], pH and PCO(2) in blood plasma because it is equilibrated with the interstitial fluid. These quantities were measured in earlobe blood during and after incremental bicycle exercise in 13 untrained (UT) and 21 endurance-trained (TR) males to find out if acute and chronic exercise influence the defense. During exercise the capacity of non-bicarbonate buffers (beta(nbi) = -Delta[La] . DeltapH(-1) - Delta[HCO(3)(-)] . DeltapH(-1)) available for the extracellular fluid (mainly hemoglobin, dissolved proteins and phosphates) amounted to 32 +/- 2(SEM) and 20 +/- 2 mmol l(-1) in UT and TR, respectively (P < 0.02). During recovery beta(nbi) decreased to 14 (UT) and 12(TR) mmol l(-1) (both P < 0.001) corresponding to values previously found at rest by in vivo CO(2) titration. Bicarbonate buffering (beta(bi)) amounted to 44-48 mmol l(-1) during and after exercise. The large exercise beta(nbi) seems to be mainly caused by an increasing concentration of all buffers due to shrinking of the extracellular volume, exchange of small amounts of HCO(3)(-) or H(+) with cells and delayed HCO(3)(-) equilibration between plasma and interstitial fluid. Increase of [HCO(3)(-)] during titration by these mechanisms augments total beta and thus the calculated beta(nbi) more than beta(bi) because it reduces DeltapH and Delta[HCO(3)(-)] at constant Delta[La]. The smaller rise in exercise beta(nbi) in TR than UT may be caused by an increased extracellular volume and an improved exchange of La(-), HCO(3)(-) and H(+) between trained muscles and blood.
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4.
Hematological and acid-base changes in men during prolonged exercise with and without sodium-lactate infusion.
Miller, BF, Lindinger, MI, Fattor, JA, Jacobs, KA, Leblanc, PJ, Duong, M, Heigenhauser, GJ, Brooks, GA
Journal of applied physiology (Bethesda, Md. : 1985). 2005;(3):856-65
Abstract
An emerging technique used for the study of metabolic regulation is the elevation of lactate concentration with a sodium-lactate infusion, the lactate clamp (LC). However, hematological and acid-base properties affected by the infusion of hypertonic solutions containing the osmotically active strong ions sodium (Na(+)) and lactate (Lac(-)) are a concern for clinical and research applications of LC. In the present study, we characterized the hematological and plasma acid-base changes during rest and prolonged, light- to moderate-intensity (55% Vo(2 peak)) exercise with and without LC. During the control (Con) trial, subjects were administered an isotonic, isovolumetric saline infusion. During LC, plasma lactate concentration ([Lac(-)]) was elevated to 4 meq/l during rest and to 4-7 meq/l during exercise. During LC at rest, there were rapid and transient changes in plasma, erythrocyte, and blood volumes. LC resulted in decreased plasma [H(+)] (from 39.6 to 29.6 neq/l) at the end of exercise while plasma [HCO(3)(-)] increased from 26 to 32.9 meq/l. Increased plasma strong ion difference [SID], due to increased [Na(+)], was the primary contributor to decreased [H(+)] and increased [HCO(3)(-)]. A decrease in plasma total weak acid concentration also contributed to these changes, whereas Pco(2) contributed little. The infusion of hypertonic LC caused only minor volume, acid-base, and CO(2) storage responses. We conclude that an LC infusion is appropriate for studies of metabolic regulation.
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5.
Short-term low-carbohydrate diet dissociates lactate and ammonia thresholds in men.
Langfort, J, Czarnowski, D, Zendzian-Piotrowska, M, Zarzeczny, R, Górski, J
Journal of strength and conditioning research. 2004;(2):260-5
Abstract
A low-carbohydrate (L-CHO) diet has been shown to shift the lactate threshold toward higher workloads. The aim of the present study was to examine the effect of an L-CHO diet on the ammonia threshold and to compare it with the lactate threshold in men. The plasma catecholamine threshold was also measured. Eight young, untrained men participated in the study. Two exercise tests with graded workload were performed. The workload was increased every 3 minutes by 40 W until volitional exhaustion. The first test was performed after 3 days of a controlled mixed diet. After the first test, the mixed diet was switched to a L-CHO diet. Three days later the same test was repeated. The blood concentration of lactate, ammonia, noradrenaline, and adrenaline was measured before and after each workload in both groups. It was found that the concentration of the examined compounds in the blood increases exponentially with graded workload after each kind of diet. This led us to calculate the blood ammonia, lactate, epinephrine, and norepinephrine thresholds. The thresholds were defined as points at which the concentration of a given compound starts to increase in a nonlinear fashion, which is calculated using 2 segmental linear regressions. After the mixed diet, the threshold for each compound occurs at the same workload. The L-CHO diet resulted in dissociation of the lactate threshold from the ammonia threshold: the lactate threshold was shifted toward a higher workload, whereas the ammonia threshold was shifted toward a lower workload. The norepinephrine threshold was also shifted toward a lower workload, and the epinephrine threshold remained unchanged. The results obtained indicate that an L-CHO diet accelerates production of ammonia and delays production of lactate during graded exercise, as well as that diet must be strictly controlled when ammonia and lactate thresholds are measured.
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6.
Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism.
Duncan, GE, Perkins, LA, Theriaque, DW, Neiberger, RE, Stacpoole, PW
The Journal of clinical endocrinology and metabolism. 2004;(4):1733-8
Abstract
We determined acute and chronic effects of dichloroacetate (DCA) on maximal (MAX) and submaximal (SUB) exercise responses in patients with abnormal mitochondrial energetics. Subjects (n = 9) completed a MAX treadmill bout 1 h after ingesting 25 mg/kg DCA or placebo (PL). A 15-min SUB bout was completed the next day while receiving the same treatment. After a 1-d washout, MAX and SUB were repeated while receiving the alternate treatment (acute). Gas exchange and heart rate were measured throughout all tests. Blood lactate (Bla) was measured 0, 3, and 10 min after MAX, and 5, 10, and 15 min during SUB. MAX and SUB were repeated after 3 months of daily DCA or PL. After a 2-wk washout, a final MAX and SUB were completed after 3 months of alternate treatment (chronic). Average Bla during SUB was lower (P < 0.05) during both acute (1.99 +/- 1.10 vs. 2.49 +/- 1.52 mmol/liter) and chronic (1.71 +/- 1.37 vs. 2.39 +/- 1.32 mmol/liter) DCA vs. PL despite similar exercise intensities between conditions ( approximately 75 and 70% maximal exercise capacity during acute and chronic treatment). Thus, although DCA does not alter MAX responses, acute and chronic DCA attenuate the Bla response to moderate exercise in patients with abnormal mitochondrial energetics.
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7.
Short-term creatine supplementation does not improve muscle activation or sprint performance in humans.
Kinugasa, R, Akima, H, Ota, A, Ohta, A, Sugiura, K, Kuno, SY
European journal of applied physiology. 2004;(2-3):230-7
Abstract
The purpose of this study was to examine the influence of short-term creatine (Cr) supplementation on exercise-induced transverse relaxation time (T2) and sprint performance during maximum intermittent cycling exercise using the muscle functional magnetic resonance imaging (mfMRI) technique. Twelve men were divided into a Cr supplementation group [the Cr group, taking 4 x (5 g Cr monohydrate + 2.5 g maltodextrin)/day], or a placebo supplementation group (the P group, taking 4 x 7.5 g maltodextrin/day). The allocation to the groups was based on cycling tests and the subject's physical characteristics, and thus was not randomized. A double-blind research design was employed for a 5-day supplementation period. mfMR images of the right thigh were collected at rest and immediately after two, five, and ten 6-s sprint bouts of maximum intermittent cycling exercise with a 30-s recovery interval between sets. Before and after supplementation, blood was taken to calculate lactate accumulation, and the muscle volume of the thigh was determined by MRI. Following supplementation, there was significant body mass gain in the Cr group ( P<0.05), whereas the P group did not change. The exercise-induced T2, blood lactate levels and sprint performance were not affected by Cr supplementation in any sprint bouts. These results suggest that short-term Cr supplementation does not influence short duration repetitive sprint performance and muscle activation and/or metabolic state during sprint cycling evaluated by mfMRI of the skeletal muscle in humans.
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Cognitive impairment is related to cerebral lactate in patients with carotid artery occlusion and ipsilateral transient ischemic attacks.
Bakker, FC, Klijn, CJ, Jennekens-Schinkel, A, van der Tweel, I, van der Grond, J, van Huffelen, AC, Tulleken, CA, Kappelle, LJ
Stroke. 2003;(6):1419-24
Abstract
BACKGROUND AND PURPOSE Patients with carotid artery occlusion (CAO) and ipsilateral transient ischemic attack (TIA) can have lasting cognitive impairment, despite the recovery of focal neurological deficits. We sought to assess whether cognitive impairment in these patients is associated with hemodynamic compromise and/or impaired cerebral metabolism. METHODS In 39 consecutive patients with a TIA associated with an angiographically proven occlusion of the carotid artery, we examined (1) cognitive functioning, (2) cerebrovascular reserve capacity of the middle cerebral artery ipsilateral to the CAO as measured by transcranial Doppler ultrasound, and (3) metabolic ratios as measured by 1H-MR spectroscopy in the centrum semiovale ipsilateral to the symptomatic CAO. Findings were compared with those in healthy control subjects. RESULTS As a group, patients were cognitively impaired. Mean CO2 reactivity and the mean ratio of N-acetyl aspartate to creatine were decreased. In approximately one third of patients, lactate was present in noninfarcted regions. The presence of lactate proved to be a stronger correlate of cognitive impairment than MRI-detected lesions (beta=0.41 versus beta=0.15). Cognitive impairment did not correlate with CO2 reactivity or the ratio of N-acetyl aspartate to creatine. CONCLUSIONS This exploratory study in patients with CAO and ipsilateral TIA showed that 1H-MR spectroscopy-detected lactate in noninfarcted regions is a better indicator of cognitive impairment than MRI-detected lesions. Cognitive impairment did not correlate with CO2 reactivity.
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9.
Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.
Bundgaard, H, Kjeldsen, K, Suarez Krabbe, K, van Hall, G, Simonsen, L, Qvist, J, Hansen, CM, Moller, K, Fonsmark, L, Lav Madsen, P, et al
American journal of physiology. Heart and circulatory physiology. 2003;(3):H1028-34
Abstract
We assessed the hypothesis that the epinephrine surge present during sepsis accelerates aerobic glycolysis and lactate production by increasing activity of skeletal muscle Na(+)-K(+)-ATPase. Healthy volunteers received an intravenous bolus of endotoxin or placebo in a randomized order on two different days. Endotoxemia induced a response resembling sepsis. Endotoxemia increased plasma epinephrine to a maximum at t = 2 h of 0.7 +/- 0.1 vs. 0.3 +/- 0.1 nmol/l (P < 0.05, n = 6-7). Endotoxemia reduced plasma K(+) reaching a nadir at t = 5 h of 3.3 +/- 0.1 vs. 3.8 +/- 0.1 mmol/l (P < 0.01, n = 6-7), followed by an increase to placebo level at t = 7-8 h. During the declining plasma K(+), a relative accumulation of K(+) was seen reaching a maximum at t = 6 h of 8.7 +/- 3.8 mmol/leg (P < 0.05). Plasma lactate increased to a maximum at t = 1 h of 2.5 +/- 0.5 vs. 0.9 +/- 0.1 mmol/l (P < 0.05, n = 8) in association with increased release of lactate from the legs. These changes were not associated with hypoperfusion or hypoxia. During the first 24 h after endotoxin infusion, renal K(+) excretion was 27 +/- 7 mmol, i.e., 58% higher than after placebo. Combination of the well-known stimulatory effect of catecholamines on skeletal muscle Na(+)-K(+)-ATPase activity, with the present confirmation of an expected Na(+)-K(+)- ATPase-induced decline in plasma K(+), suggests that the increased lactate release was due to increased Na(+)-K(+)-ATPase activity, supporting our hypothesis. Thus increased lactate levels in acutely and severely ill patients should not be managed only from the point of view that it reflects hypoxia.
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10.
Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis.
Dratwa, M, Wilkie, M, Ryckelynck, JP, ter Wee, PM, Rutherford, P, Michel, C, Hopwood, A, Curtis, L, Denys, N, Divino Filho, JC, et al
Kidney international. Supplement. 2003;(88):S105-13
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Abstract
UNLABELLED Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis. BACKGROUND Patients on automated peritoneal dialysis (APD) usually receive larger volumes of dialysis solution and more frequent, shorter exchanges than patients on continuous ambulatory peritoneal dialysis (CAPD), and therefore are likely to derive greater benefit from more physiologic solutions. METHODS Peritoneal dialysis solutions containing 25 mmol/L bicarbonate and either 10 or 15 mmol/L lactate were compared with standard lactate solutions (35 or 40 mmol/L) in two prospective, open-label studies of patients on APD. Each study included a 2-week baseline period (lactate solution), a 6-week treatment period (bicarbonate/lactate solution), and a 2-week follow-up period (same lactate solution as baseline). Biochemical analyses and assessments of vital signs and safety parameters were conducted at baseline, every 2 weeks during treatment, and at the end of the follow-up period. A product use questionnaire was administered in one study at the end of treatment. RESULTS A statistically significant rise in plasma bicarbonate (approximately 2 mmol/L) occurred when patients switched from a lactate solution to the bicarbonate/lactate solution with equimolar buffer concentration (P < 0.001 for each solution). Plasma bicarbonate decreased by 1.16 mmol/L after a switch from lactate 40 mmol/L to bicarbonate/lactate 35 mmol/L (P < 0.001). When patients switched to bicarbonate/lactate 35, the majority of individual venous plasma bicarbonate values were in the normal range. A switch from a lower calcium (1.25 mmol/ L) lactate solution to a higher calcium (1.75 mmol/L) lactate/bicarbonate solution resulted in a statistically significant rise in serum calcium (0.06 mmol/L, P < 0.018). The product use questionnaire revealed improvements in symptoms, including reduced pain on infusion. CONCLUSION Bicarbonate/lactate solutions may be used safely and effectively in patients on APD. The availability of 2 formulations with different buffer and calcium content provides flexibility for the control of acidosis as well as calcium balance.