Histamine H
            <sub>1</sub>
            and H
            <sub>2</sub>
            receptors are essential transducers of the integrative exercise training response in humans

Stede, Thibaux Van der; Blancquaert, Laura; Stassen, Flore; Everaert, Inge; Thienen, Ruud Van; Vervaet, Chris; Gliemann, Lasse; Hellsten, Ylva; Derave, Wim

doi:10.1126/sciadv.abf2856

Cited by 21 publications

(24 citation statements)

References 60 publications

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“…Importantly, they also found that several histamine receptormediated adaptations were interrelated, as increases in VO 2max were related to changes in vascular function and whole-body insulin sensitivity. Moreover, a correlation was found between changes in capillary-fiber ratio and whole-body insulin sensitivity (Van der Stede et al, 2021). These findings are consistent with recent research suggesting that the post-exercise activation of H 1 -and H 2 -receptors upregulate several related pathways, including those related to metabolism, endothelial and vascular function (Romero et al, 2016), thereby highlighting important histaminergic adaptations to exercise that potentially impact both post-exercise blood flow and metabolic regulation.…”

Section: Discussion: Future Directionssupporting

confidence: 90%

“…In addition to investigations examining the acute effects of post-exercise vasodilation on glucose regulation, future investigations are needed to examine emerging interactions between vascular and metabolic adaptions to exercise. Along those lines, Van der Stede et al (2021) observed that histamine receptor blockade blunted post-exercise muscle perfusion and increases in whole body insulin sensitivity in response to 6 weeks of high-intensity interval training in healthy males. Importantly, they also found that several histamine receptormediated adaptations were interrelated, as increases in VO 2max were related to changes in vascular function and whole-body insulin sensitivity.…”

Section: Discussion: Future Directionsmentioning

confidence: 90%

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Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Pellinger

Emhoff

2022

Front. Physiol.

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For both healthy individuals and patients with type 2 diabetes (T2D), the hemodynamic response to regular physical activity is important for regulating blood glucose, protecting vascular function, and reducing the risk of cardiovascular disease. In addition to these benefits of regular physical activity, evidence suggests even a single bout of dynamic exercise promotes increased insulin-mediated glucose uptake and insulin sensitivity during the acute recovery period. Importantly, post-exercise hypotension (PEH), which is defined as a sustained reduction in arterial pressure following a single bout of exercise, appears to be blunted in those with T2D compared to their non-diabetic counterparts. In this short review, we describe research that suggests the sustained post-exercise vasodilation often observed in PEH may sub-serve glycemic regulation following exercise in both healthy individuals and those with T2D. Furthermore, we discuss the interplay of enhanced perfusion, both macrovascular and microvascular, and glucose flux following exercise. Finally, we propose future research directions to enhance our understanding of the relationship between post-exercise hemodynamics and glucose regulation in healthy individuals and in those with T2D.

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Section: Discussion: Future Directionssupporting

confidence: 90%

Section: Discussion: Future Directionsmentioning

confidence: 90%

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Pellinger

Emhoff

2022

Front. Physiol.

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“…For instance, the exercise-induced increase in glucose uptake is dependent on an increase in blood perfusion ( McConell et al., 2020 ). Moreover, inhibition of vasodilation and angiogenesis in response to exercise impaired exercise-induced increases in performance ( Van der Stede et al., 2021 ). We did not observe a difference in performance, muscle oxidative parameters, or fiber-type changes.…”

Section: Discussionmentioning

confidence: 99%

Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells

et al. 2021

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Summary Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms of exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary muscle endothelial cell (mEC) populations that are characterized by differential expression of ATF3/4. Spatial mapping showed that ATF3/4 + mECs are enriched in red oxidative muscle areas while ATF3/4 low ECs lie adjacent to white glycolytic fibers. In vitro and in vivo experiments revealed that red ATF3/4 + mECs are more angiogenic when compared with white ATF3/4 low mECs. Mechanistically, ATF3/4 in mECs control genes involved in amino acid uptake and metabolism and metabolically prime red (ATF3/4 + ) mECs for angiogenesis. As a consequence, supplementation of non-essential amino acids and overexpression of ATF4 increased proliferation of white mECs. Finally, deleting Atf4 in ECs impaired exercise-induced angiogenesis. Our findings illustrate that spatial metabolic angiodiversity determines the angiogenic potential of muscle ECs.

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“…The sample volume was maximized to the artery diameter with care taken to avoid interference of the vessel walls and a standard low-velocity rejection filter was applied. Femoral artery diameter was determined in triplicate during systole with the built-in calipers [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

The ergogenic effect of acute carnosine and anserine supplementation: dosing, timing, and underlying mechanism

Jager

Blancquaert

Stede

et al. 2022

Journal of the International Society of Sports Nutrition

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Background Recent studies suggest that acute-combined carnosine and anserine supplementation has the potential to improve the performance of certain cycling protocols. Yet, data on optimal dose, timing of ingestion, effective exercise range, and mode of action are lacking. Three studies were conducted to establish dosing and timing guidelines concerning carnosine and anserine intake and to unravel the mechanism underlying the ergogenic effects. Methods First, a dose response study A was conducted in which 11 men randomly received placebo, 10, 20, or 30 mg.kg −1 of both carnosine and anserine. They performed 3x maximal voluntary isometric contractions (MVC), followed by a 5 x 6 s repeated cycling sprint ability test (RSA), once before the supplement and 30 and 60 minutes after. In a second study, 15 men performed 3x MVCs with femoral nerve electrical stimulation, followed by an RSA test, once before 30 mg.kg −1 carnosine and anserine and 60 minutes after. Finally, in study C, eight men performed a high intensity cycling training after randomly ingesting 30 mg.kg −1 of carnosine and anserine, a placebo or antihistamines (reduce post-exercise blood flow) to investigate effects on muscle perfusion. Results Study A showed a 3% peak power (p = 0.0005; 95% CI = 0.07 to 0.27; ES = 0.91) and 4.5% peak torque (p = 0.0006; 95% CI = 0.12 to 0.50; ES = 0.87) improvement on RSA and MVC, with 30 mg.kg −1 carnosine + anserine ingestion 60 minutes before the performance yielding the best results. Study B found no performance improvement on group level; however, a negative correlation (r = −0.54; p = 0.0053; 95% CI = −0.77 to −0.19) was found between carnosinase enzyme activity (responsible for carnosine and anserine breakdown) and performance improvement. No effect of the supplement on neuromuscular function nor on muscle perfusion was found. Conclusions These studies reveal that acute ingestion of 30 mg.kg −1 of both carnosine and anserine, 60 minutes before a high intensity exercise, can potentially improve performance, such as short cycling sprints or maximal muscle contractions. Subjects with lower carnosinase activity, and thus a slower breakdown of circulating dipeptides, appear to benefit more from this ergogenic effect. Finally, neither the involvement of a direct effect on neuromuscular function, nor an indirect effect on recovery through increased muscle perfusion could be confirmed as potential mechanism of action. The ergogenic mechanism therefore remains elusive.

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Histamine H ₁ and H ₂ receptors are essential transducers of the integrative exercise training response in humans

Cited by 21 publications

References 60 publications

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells

The ergogenic effect of acute carnosine and anserine supplementation: dosing, timing, and underlying mechanism

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Histamine H 1 and H 2 receptors are essential transducers of the integrative exercise training response in humans

Cited by 21 publications

References 60 publications

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation

Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells

The ergogenic effect of acute carnosine and anserine supplementation: dosing, timing, and underlying mechanism

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Product

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Histamine H ₁ and H ₂ receptors are essential transducers of the integrative exercise training response in humans