Preventive effects of low‐intensity endurance exercise for severe hyperglycemia‐induced capillary regression in non‐obese type 2 diabetes rat skeletal muscle

Morifuji, Takeshi; Tanaka, Minoru; Nakanishi, Ryosuke; Hirabayashi, Tamio; Kondo, Hiroyo; Fujino, Hidemi

doi:10.14814/phy2.14712

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…Decreased perfusion in the hindlimb in spite of maintained vasodilatation in resistance arteries–arterioles conceivably might be related to decreased capillary network density that has been found in diabetic animals (Morifuji et al ., 2021) (Fig. 9) or limited by perfusion into a shunt (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…This impairment in perfusion in fa/fa rats were also supported by the data obtained using direct blood flow measurement of the conduit femoral artery in the present study. Decreased perfusion in the hindlimb in spite of maintained vasodilatation in resistance arteries-arterioles conceivably might be related to decreased capillary network density that has been found in diabetic animals (Morifuji et al, 2021) (Fig. 9) or limited by perfusion into a shunt (e.g.…”

Section: Visualized Dynamic Changes In Rat Hindlimb Arterial Tree Res...mentioning

confidence: 91%

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Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats

Sonobe

Tsuchimochi

Maeda

et al. 2022

The Journal of Physiology

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In resistance arteries, endothelium‐dependent hyperpolarization (EDH)‐mediated vasodilatation is depressed in diabetes. We hypothesized that downregulation of KCa channel derived EDH reduces exercise‐induced vasodilatation and blood flow redistribution in diabetes. To test this hypothesis, we evaluated vascular function in response to hindlimb muscle contraction, and the contribution of KCa channels in anaesthetised ZFDM, metabolic disease rats with type 2 diabetes. We also tested whether exercise training ameliorated the vascular response. Using in vivo microangiography, the hindlimb vasculature was visualized before and after rhythmic muscle contraction (0.5 s tetanus every 3 s, 20 times) evoked by sciatic nerve stimulation (40 Hz). Femoral blood flow of the contracting hindlimb was simultaneously measured by an ultrasonic flowmeter. The contribution of KCa channels was investigated in the presence and absence of apamin and charybdotoxin. We found that vascular and blood flow responses to muscle contraction were significantly impaired at the level of small artery segments in ZFDM fa/fa rats compared to its lean control fa/+ rats. The contribution of KCa channels was also smaller in fa/fa than in fa/+ rats. Low‐intensity exercise training for 12 weeks in fa/fa rats demonstrated minor changes in the vascular and blood flow response to muscle contraction. However, the KCa‐derived component in the response to muscle contraction was much greater in exercise trained than in sedentary fa/fa rats. These data suggest that exercise training increases the contribution of KCa channels among endothelium‐dependent vasodilatory mechanisms to maintain vascular and blood flow responses to muscle contraction in this metabolic disease rat model. Key points Microvascular dysfunction in type 2 diabetes impairs blood flow redistribution during exercise and limits the performance of skeletal muscle and may cause early fatigability. Endothelium‐dependent hyperpolarization (EDH), which mediates vasodilatation in resistance arteries, is known to be depressed in animals with diabetes. Here, we report that low‐intensity exercise training in ZFDM rats increased the KCa channel‐derived component in the vasodilator responses to muscle contraction compared to that in sedentary rats, partly as a result of the increase in KCNN3 expression. These results suggest that low‐intensity exercise training improves blood flow redistribution in contracting skeletal muscle in metabolic disease with diabetes via upregulation of EDH.

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Section: Discussionmentioning

confidence: 99%

Section: Visualized Dynamic Changes In Rat Hindlimb Arterial Tree Res...mentioning

confidence: 91%

Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats

Sonobe

Tsuchimochi

Maeda

et al. 2022

The Journal of Physiology

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Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice

Tanaka,

Sugimoto,

Akasaka

et al. 2024

American Journal of Physiology-Endocrinology and Metabolism

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This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

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Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats

Tanaka

Morifuji

Sugimoto

et al. 2021

Journal of Applied Physiology

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To clarify the preventive effects of low current electrical stimulation (ES) under blood flow restriction (Bfr) on diabetes-associated capillary regression in skeletal muscles, we assessed the changes in three-dimensional capillary architecture and angiogenic factors. Twenty-four Goto-Kakizaki rats were randomly divided into four groups: the sedentary diabetes mellitus (DM), Bfr (DM+Bfr), electrical stimulation (DM+ES), and Bfr plus ES (DM+Bfr+ES) groups. Six healthy Wistar rats were used as age-matched controls. Bfr was performed using pressure cuffs (80 mmHg) around the thighs of the rats, and low-current ES was applied to the calf muscles of the rats. The current intensity was set at 30% of the maximal isometric contraction (24-30 mA). The treatments were delivered three times a week for eight weeks. In the DM group, the capillary diameter and volume of the soleus muscle decreased, and, the anti-angiogenic factor level increased. Furthermore, DM caused an increase in the hypoxia-inducible factor. Individually, Bfr or ES treatments failed to inhibit the DM-associated capillary regression and increase in anti-angiogenic factor. However, combined treatment with Bfr and ES prevented DM-associated capillary regression via inhibition of the increased anti-angiogenic factor and enhancement of interleukin-15 expression, mitochondrial biogenesis factors, and a pro-angiogenic factor. Therefore, DM-associated capillary regression inhibited by the combined treatment may prevent the effects of the increased anti-angiogenic factor and enhance the pro-angiogenic factor.

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Preventive effects of low‐intensity endurance exercise for severe hyperglycemia‐induced capillary regression in non‐obese type 2 diabetes rat skeletal muscle

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 3 publications

References 54 publications

Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats

Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice

Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats

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