Shinichiro Murakami

Protective effects of astaxanthin on capillary regression in atrophied soleus muscle of rats

The capillary regression in skeletal muscles associated with a chronic decrease in activity is related to a dysfunction of endocapillary cells induced by over‐expression of oxidative stress. We hypothesized that treatment with astaxanthin, an antioxidant, would attenuate the oxidative stress induced by decreased skeletal muscle use, and that this attenuation would prevent the associated capillary regression. The purpose of the present study was to investigate the antioxidant and preventive effects of astaxanthin on capillary regression in the soleus muscle during hindlimb unloading.

Protective effects of exercise preconditioning on hindlimb unloading-induced atrophy of rat soleus muscle

Aim:  A chronic decrease in the activation and loading levels of skeletal muscles as occurs with hindlimb unloading (HU) results in a number of detrimental changes. Several proteolytic pathways are involved with an increase in myofibrillar protein degradation associated with HU. Exercise can be used to counter this increase in proteolytic activity and, thus, may be able to protect against some of the detrimental changes associated with chronic decreased use. The purpose of the present study was to determine the potential of a single bout of preconditioning endurance exercise in attenuating the effects of 2 weeks of HU on the mass, phenotype and force‐related properties of the soleus muscle in adult rats.

Effects of Hyperbaric Oxygen on Metabolic Capacity of the Skeletal Muscle in Type 2 Diabetic Rats with Obesity

We investigated whether hyperbaric oxygen enhances the oxidative metabolic capacity of the skeletal muscle and attenuates adipocyte hypertrophy in type 2 diabetic rats with obesity. Five-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as diabetic animals and nondiabetic controls, respectively, and assigned to control and hyperbaric oxygen groups. Animals in the hyperbaric oxygen group were exposed to an atmospheric pressure of 1.25 with an oxygen concentration of 36% for 3 h daily. The glucose level at 27 weeks of age was significantly higher in OLETF rats than in LETO rats, but the elevation was inhibited in OLETF rats exposed to hyperbaric oxygen. The slow-to-fast fiber transition in the skeletal muscle was observed in OLETF rats, but the shift was inhibited in OLETF rats exposed to hyperbaric oxygen. Additionally, the oxidative enzyme activity of muscle fibers was increased by hyperbaric oxygen. The adipocyte size was larger in OLETF rats than in LETO rats, but hypertrophied adipocytes were not observed in OLETF rats exposed to hyperbaric oxygen. Hyperbaric oxygen enhances glucose and lipid metabolism in the skeletal muscle, indicating that hyperbaric oxygen can prevent elevation of glucose and adipocyte hypertrophy in diabetic rats with obesity.

Differences in capillary architecture, hemodynamics, and angiogenic factors in rat slow and fast plantarflexor muscles

The capillary architecture in skeletal muscles is unique in that it has anastomoses that interconnect individual capillaries.

Amelioration of capillary regression and atrophy of the soleus muscle in hindlimb‐unloaded rats by astaxanthin supplementation and intermittent loading

What is the central question of this study? We asked whether the combination of astaxanthin supplementation and intermittent loading would attenuate both the muscle atrophy and the capillary regression associated with chronic unloading. What is the main finding and its importance? Intermittent loading alone attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network in the soleus. The combination of these two interventions ameliorated both the muscle atrophy and the capillary regression induced by chronic unloading.

The Combined Effect of Electrical Stimulation and High-Load Isometric Contraction on Protein Degradation Pathways in Muscle Atrophy Induced by Hindlimb Unloading

High-load isometric exercise is considered an effective countermeasure against muscle atrophy, but therapeutic electrical stimulation for muscle atrophy is often performed without loading. In the present study, we investigated the combined effectiveness of electrical stimulation and high-load isometric contraction in preventing muscle atrophy induced by hindlimb unloading. Electrical stimulation without loading resulted in slight attenuation of muscle atrophy. Moreover, combining electrical stimulation with high-load isometric contraction enhanced this effect. In electrical stimulation without loading, inhibition of the overexpression of calpain 1, calpain 2, and MuRF-1 mRNA was confirmed. On the other hand, in electrical stimulation with high-load isometric contraction, inhibition of the overexpression of cathepsin L and atrogin-1 mRNA in addition to calpain 1, calpain 2, and MuRF-1 mRNA was confirmed. These findings suggest that the combination of electrical stimulation and high-load isometric contraction is effective as a countermeasure against muscle atrophy.

Abnormalities in the Fiber Composition and Capillary Architecture in the Soleus Muscle of Type 2 Diabetic Goto-Kakizaki Rats

Type 2 diabetes mellitus is linked to impaired skeletal muscle glucose uptake and storage. This study aimed to investigate the fiber type distributions and the three-dimensional (3D) architecture of the capillary network in the skeletal muscles of type 2 diabetic rats. Muscle fiber type transformation, succinate dehydrogenase (SDH) activity, capillary density, and 3D architecture of the capillary network in the soleus muscle were determined in 36-week-old Goto-Kakizaki (GK) rats as an animal model of nonobese type 2 diabetes and age-matched Wistar (Cont) rats. Although the soleus muscle of Cont rats comprised both type I and type IIA fibers, the soleus muscle of GK rats had only type I fibers. In addition, total SDH activity in the soleus muscle of GK rats was significantly lower than that in Cont rats because GK rats had no high-SDH activity type IIA fiber in the soleus muscle. Furthermore, the capillary diameter, capillary tortuosity, and microvessel volume in GK rats were significantly lower than those in Cont rats. These results indicate that non-obese diabetic GK rats have muscle fiber type transformation, low SDH activity, and reduced skeletal muscle capillary content, which may be related to the impaired glucose metabolism characteristic of type 2 diabetes.

Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes

Based on findings obtained using two-dimensional capillary analyses on tissue cross-sections, diabetes has been shown to be associated with a high risk for microangiopathy and capillary regression in skeletal muscles. We visualized the three-dimensional architecture of the capillary networks in the soleus muscle of non-obese Goto-Kakizaki (GK) rats with type 2 diabetes and compared them with those of control Wistar rats to provide novel information, e.g., capillary volume, on the capillary networks. In addition, we examined pro- and anti-angiogenic gene expression levels in the soleus muscle of GK rats using TaqMan probe-based real-time PCR. As expected, plasma glucose levels were higher and insulin levels lower in GK than control rats. The three-dimensional architecture of the capillary networks was regressed and capillary volume was smaller in the soleus muscle of GK compared to control rats. The mRNA expression levels of the pro-angiogenic factors HIF-1α, KDR, Flt-1, ANG-1, and Tie-2 were lower, whereas the level of the anti-angiogenic factor TSP-1 was higher in GK than control rats. These data suggest that a decrease in pro-angiogenic and increase in anti-angiogenic factors may play an important role in type 2 diabetes-induced muscle circulatory complications.

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

Introduction: We determined the effects of low‐intensity exercise on the three‐dimensional capillary structure and associated angiogenic factors in the soleus muscle of Goto‐Kakizaki (GK) diabetic rats. Methods: Four groups of male rats were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex), sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were subjected to chronic low‐intensity running on a treadmill (15 m/min, 60 min/session, 5 sessions/week for 3 weeks). Results: Although mean capillary volume and diameter were lower in the GK compared with all other groups, low‐intensity exercise increased both of these measures in GK rats. Mitochondrial markers, i.e., SDH activity and PGC‐1α expression, and the levels of angiogenic factors were higher in the GK+Ex than all other groups. Exercise increased vascular endothelial growth factor (VEGF) protein levels and the VEGF‐to‐TSP‐1 ratio, an indicator of angiogenesis, in GK rats. Conclusions: Combined, the results indicate that low‐intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles. Muscle Nerve 51: 391–399, 2015

Exercise Training Prevents Decrease in Luminal Capillary Diameter of Skeletal Muscles in Rats with Type 2 Diabetes

The purpose of this study was to examine whether exercise training can prevent microangiopathy of skeletal muscles in rats with type 2 diabetes and if succinate dehydrogenase (SDH) activity, an indicator of mitochondrial oxidative enzyme activity, is involved in the prevention of microangiopathy. Six-week-old male Goto-Kakizaki (GK) rats and age-matched male Wistar rats (control group (Con)) were used. GK rats were randomly assigned to nonexercise (DB) and exercise (DBEx) groups. The DBEx group was trained on a treadmill 5 times a week for 3 weeks. No significant differences in the capillary-to-fibre ratio or the capillary density were observed between the 3 groups. The luminal capillary diameter of the DB group was significantly lower than that of the Con group, whereas the capillary diameter of the DBEx group was significantly higher than that of the DB group. In addition, SDH activity was significantly higher in the DBEx group than in the Con and DB groups. Microangiopathy of skeletal muscles in type 2 diabetes was correlated with a decrease in the luminal capillary diameter, which was prevented by exercise training. Thus, the mitochondrial oxidative capacity appears to be involved in the overall mechanism by which exercise prevents microangiopathy.