Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele

Flück, Martin; Vaughan, David; Rittweger, Jörn; Giraud, M

doi:10.3389/fphys.2022.933792

Cited by 2 publications

(2 citation statements)

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“…Conversely, our findings on differences in the AUC of blood glucose concentration and AUC of heart rate (per delivered muscle work) between carriers and non-carriers of the ACE I-allele during ramp exercise and subsequent recovery confirm the reported association of variability in aspects of cardiovascular functioning with the ACE-I/D genotype [3,32]. We have recently reported that the biochemical processes involved in glucose uptake into muscle fibers are reduced in the ACE-DD genotypes in correspondence with elevated levels of angiotensin 2 [22]. This suggests that the training resistance of blood glucose concentration may be related to the persistent influence of different levels of angiotensin signaling in the capillary bed that supplies muscle fibers.…”

Section: Discussionsupporting

confidence: 74%

“…The expectation based on the literature was that the ACE I-allele carriers would demonstrate stronger improvements in aerobic muscle metabolism with training due to better perfusion, i.e., higher total hemoglobin content, during exercise and a faster and more complete replenishment of muscle oxygen saturation with the cessation of exercise after exhaustion. Conversely, we assumed that the cardiovascular aspects would be directly related to cardiac output and that the glucose uptake into skeletal muscle [10,11,22] would be worse in non-carriers of the ACE I-allele, but would eventually improve in the course of training owing to the repeated challenge to cardiometabolic and -vascular function during exercise. As a hypothesis with potential falsification, it shall be stated that no association between the ACE gene polymorphism and the training answer can be detected [23].…”

Section: Introductionmentioning

confidence: 99%

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ACE-I/D Allele Modulates Improvements of Cardiorespiratory Function and Muscle Performance with Interval-Type Exercise

Gasser

Niederseer

Frey³

et al. 2023

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Background: The prominent insertion/deletion polymorphism in the gene for the major modulator of tissue perfusion, angiotensin-converting enzyme (ACE-I/D) is associated with variability in adjustments in cardiac and skeletal muscle performance with standard forms of endurance and strength type training. Here, we tested whether the ACE-I/D genotype would be associated with variability in the effects of interval-type training on peak and aerobic performance of peripheral muscle and cardio-vasculature and post-exercise recovery. Methods: Nine healthy subjects (39.0 ± 14.7 years of age; 64.6 ± 16.1 kg, 173.6 ± 9.9) completed eight weeks of interval training on a soft robotic device based on repeated sets of a pedaling exercise at a matched intensity relative to their peak aerobic power output. Prior to and post-training, peak anaerobic and aerobic power output was assessed, mechanical work and metabolic stress (oxygen saturation and hemoglobin concentrations of Musculus vastus lateralis (VAS) and Musculus gastrocnemius (GAS), blood lactate and factors setting cardiac output such as heart rate, systolic and diastolic blood pressure were monitored during ramp-incremental exercise and interval exercise with the calculation of areas under the curve (AUC), which were put in relation to the produced muscle work. Genotyping was performed based on I- and D-allele-specific polymerase chain reactions on genomic DNA from mucosal swaps. The significance of interaction effects between training and ACE I-allele on absolute and work-related values was assessed with repeated measures ANOVA. Results: Subjects delivered 87% more muscle work/power, 106% more cardiac output, and muscles experienced ~72% more of a deficit in oxygen saturation and a ~35% higher passage of total hemoglobin during single interval exercise after the eight weeks of training. Interval training affected aspects of skeletal muscle metabolism and performance, whose variability was associated with the ACE I-allele. This concerned the economically favorable alterations in the work-related AUC for the deficit of SmO2 in the VAS and GAS muscles during the ramp exercise for the I-allele carriers and opposing deteriorations in non-carriers. Conversely, oxygen saturation in the VAS and GAS at rest and during interval exercise was selectively improved after training for the non-carriers of the I-allele when the AUC of tHb per work during interval exercise deteriorated in the carriers. Training also improved aerobic peak power output by 4% in the carriers but not the non-carriers (p = 0.772) of the ACE I-allele while reducing negative peak power (−27.0%) to a lesser extent in the ACE I-allele carriers than the non-carriers. Variability in cardiac parameters (i.e., the AUC of heart rate and glucose during ramp exercise, was similar to the time to recovery of maximal tHb in both muscles after cessation of ramp exercise, only associated with the ACE I-allele but not training per se. Diastolic blood pressure and cardiac output during recovery from exhaustive ramp exercise demonstrated a trend for training-associated differences in association with the ACE I-allele. Discussion: The exercise-type dependent manifestation of antidromic adjustments in leg muscle perfusion and associated local aerobic metabolism between carriers and non-carriers of the ACE I-allele with the interval-training highlight that non-carriers of the I-allele do not present an essential handicap to improve perfusion-related aerobic muscle metabolism but that the manifestation of responsiveness depends on the produced work. Conclusions: The deployed interval-type of exercise produced ACE I-allele-related differences in the alterations of negative anaerobic performance and perfusion-related aerobic muscle metabolism, which manifestation is exercise specific. The training-invariant ACE I-allele-associated differences in heart rate and blood glucose concentration emphasize that the repeated impact of the interval stimulus, despite a near doubling of the initial metabolic load, was insufficient to overturn ACE-related genetic influences on cardiovascular function.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

ACE-I/D Allele Modulates Improvements of Cardiorespiratory Function and Muscle Performance with Interval-Type Exercise

Gasser

Niederseer

Frey³

et al. 2023

Genes

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T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise

Gasser,

Dössegger,

Giraud

et al. 2024

Genes

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Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

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Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele

Cited by 2 publications

References 64 publications

ACE-I/D Allele Modulates Improvements of Cardiorespiratory Function and Muscle Performance with Interval-Type Exercise

ACE-I/D Allele Modulates Improvements of Cardiorespiratory Function and Muscle Performance with Interval-Type Exercise

T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise

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