Low‐intensity running exercise enhances the capillary volume and pro‐angiogenic factors in the soleus muscle of type 2 diabetic rats

Kondo, Hiroyo; Fujino, Hidemi; Murakami, Shinichiro; Tanaka, Masayuki; Kanazashi, Miho; Nagatomo, Fumiko; Ishihara, Akihiko; Roy, Roland R.

doi:10.1002/mus.24316

Cited by 27 publications

(46 citation statements)

References 51 publications

(105 reference statements)

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“…In this regard, exercise intervention studies would be very useful. Our study provided clear evidence of reduced oxidative enzyme activity levels and capillary regression in the skeletal muscle of diabetic cases 8) . In addition, exercise is effective in maintaining and improving oxidative metabolism in skeletal muscle.…”

Section: Diabetes-induced Capillary Regression and Protective Effectssupporting

confidence: 54%

“…Skeletal muscle of diabetes has been associated with a reduction in capillary diameter, capillary/fiber ratio, and reduced capillary diffusing capacity in animal models of diabetes 37,38) . In addition, we demonstrated regression of the capillary network in skeletal muscle with diabetes, e.g., decreased diameter, tortuosity and volume, using a three-dimensional visualizing method 7,8,39,40) . Therefore, regression of the capillary network in skeletal muscle caused by diabetes can negatively impact O2 exchange, and consequently may play a role in diabetic complications.…”

Section: Diabetes-induced Capillary Regression and Protective Effectsmentioning

confidence: 92%

“…It is known that skeletal muscle in animal and human subjects with diabetes has impaired angiogenesis and a reduced capillary network 7,8,37,47,56) . In addition, several studies have shown that diabetes affects the expression of several genes involved in angiogenesis in skeletal muscle.…”

Section: Angiogenic Factors In Disused and Diabetic Skeletal Musclesmentioning

confidence: 99%

“…In addition, structural or functional impairment within the capillary network of skeletal muscle is caused by disease. For example, diabetes affects the capillary network, e.g., a reduction in capillary number, diameter, and capillary volume in skeletal muscle 7,8) . These responses are controlled by a balance between pro-and anti-angiogenic factors and their receptors 9) .…”

Section: Introductionmentioning

confidence: 99%

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Capillary growth and regression in skeletal muscle

Fujino

Kondo

Nagatomo

et al. 2014

JPFSM

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A muscle capillary network is composed of capillaries and anastomoses, and can be modulated under varying conditions. Although exercise induces growth in the capillary network in healthy individuals, physical deconditioning and diabetes cause regression in the capillary network of skeletal muscle. Vascular endothelial growth factor (VEGF) is a critical factor in maintaining the capillary network in skeletal muscle. In addition, the angiopoietin system, is a second family of essential growth factors, that has been identified. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important angiogenic factors that bind to their common receptor Tie-2 and assist in vascular development and remodeling. Recent studies have demonstrated the contribution of anti-angiogenic factors in controlling angiogenesis in skeletal muscle. Thrombospondin-1 (TSP-1) was shown to be an angiogenesis inhibitor. A balance between pro-and anti-angiogenic factors tightly modulates capillary regression or growth. A chronic decrease in loading and activity resulted in a regression in the capillary network. We have recently shown that the levels of Ang-1 were lower, while levels of Ang-2 were unaffected in atrophied skeletal muscle. Accordingly, the Ang-2/Ang-1 ratio was higher. In addition, the VEGF/TSP-1 ratio was lower. Thus, capillary regression and growth are associated with complex pro-and anti-angiogenic factors in skeletal muscle. Meanwhile, exercise prevents capillary regression associated with a balance between pro-and anti-angiogenic factors in impaired skeletal muscle. Our study provided clear evidence of reduced oxidative enzyme activity levels and capillary regression in skeletal muscle of diabetes. Therefore, exercise has high potential for preventing capillary regression in impaired muscle.

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Section: Diabetes-induced Capillary Regression and Protective Effectssupporting

confidence: 54%

Section: Diabetes-induced Capillary Regression and Protective Effectsmentioning

confidence: 92%

Section: Angiogenic Factors In Disused and Diabetic Skeletal Musclesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Capillary growth and regression in skeletal muscle

Fujino

Kondo

Nagatomo

et al. 2014

JPFSM

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“…Gene expression analysis was conducted as previously described in Kondo et al (21). Briefly, total RNA was extracted from 30 mg of the frozen tissue samples.…”

Section: Gene Expression Analysismentioning

confidence: 99%

Preventive effects of low‐intensity exercise on cancer cachexia–induced muscle atrophy

et al. 2019

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We hypothesized that low‐intensity endurance exercise might be more effective in preventing cancer cachexia–induced muscle atrophy through both an increase in protein synthesis and a decrease in protein degradation. The purpose of present study was to evaluate the effects and to clarify the mechanism of low‐intensity endurance exercise on cancer cachexia–induced muscle atrophy. Twenty‐four male Wistar rats were randomly divided into 4 groups: control (Cont), Cont plus exercise (Ex), AH130‐induced cancer cachexia (AH130), and AH130 plus Ex. Cancer cachexia was induced by intraperitoneal injections with AH130 Yoshida ascites hepatoma cells; we analyzed the changes in muscle mass and the gene and protein expression levels of major regulators or indicators of skeletal muscle protein degradation and synthesis pathway in the soleus muscles. Low‐intensity exercise inhibited the muscle mass loss through a suppression of the ubiquitin‐proteasome pathway, increased hypoxia‐inducible factor‐1α and phosphorylated AMPK, and inhibited the deactivation of mammalian target of rapamycin pathway in the soleus muscle, which contributed to the prevention of cancer cachexia–induced muscle atrophy. These results suggest that low‐intensity exercise has the potential to become an effective therapeutic intervention for the prevention of cancer cachexia–induced muscle atrophy.—Tanaka, M., Sugimoto, K., Fujimoto, T., Xie, K., Takahashi, T., Akasaka, H., Kurinami, H., Yasunobe, Y., Matsumoto, T., Fujino, H., Rakugi, H. Preventive effects of low‐intensity exercise on cancer cachexia–induced muscle atrophy. FASEB J. 33, 7852–7862 (2019). http://www.fasebj.org

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Time course of capillary regression and an expression balance between vascular endothelial growthfactor‐Aand thrombospondin‐1 in the soleus muscle of hindlimb unloaded rats

et al. 2022

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Introduction/Aims: Skeletal muscle capillaries regress with disuse; however, information on time-dependent changes in the expression of pro-and anti-angiogenic factors in disused muscle is limited. This study aimed to clarify time-dependent changes in skeletal muscle capillarization, pro-angiogenic vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic thrombospondin-1 (TSP-1) in the soleus muscle of hindlimb unloaded rat.Methods: Eight-week-old male Sprague Dawley rats were randomly divided into four groups corresponding to different hindlimb unloading (HU) duration at 0, 1, 2, and 3 wk.Results: Muscle atrophy and capillary regression worsened in the soleus muscle with longer periods of HU. The VEGF-A protein expression level was lower at week 1 than at week 0. In addition, the value at week 3 was also lower than those at weeks 0, 1, and 2. The TSP-1 protein expression level was higher at week 1 than that at week 0 but was similar at weeks 2 and 3. Moreover, reactive oxygen species, assessed by dihydroethidium fluorescence intensity on cryosection, were higher at weeks 2 and 3 than that at week 0.Discussion: Depending on the HU period, VEGF-A and TSP-1 showed different expression patterns. In the early HU phase, TSP-1 may play an important role in capillary regression. However, when HU extends for a longer period, decreased VEGF-A, and/or increased oxidative stress may be more involved in capillary regression.

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Low‐intensity running exercise enhances the capillary volume and pro‐angiogenic factors in the soleus muscle of type 2 diabetic rats

Abstract: Combined, the results indicate that low-intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles.

Cited by 27 publications

References 51 publications

Capillary growth and regression in skeletal muscle

Capillary growth and regression in skeletal muscle

Preventive effects of low‐intensity exercise on cancer cachexia–induced muscle atrophy

Time course of capillary regression and an expression balance between vascular endothelial growthfactor‐Aand thrombospondin‐1 in the soleus muscle of hindlimb unloaded rats

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