Fumiko Nagatomo

Hyperbaric oxygen exposure improves blood glucose level and muscle oxidative capacity in rats with type 2 diabetes.

BACKGROUND The effects of exposure to hyperbaric oxygen on blood glucose level and muscle oxidative capacity in rats with type 2 diabetes were investigated. METHODS Five-week-old male Goto-Kakizaki rats were divided into four groups: normobaric (NN; exposed to 21% oxygen at 760 mm Hg for 8 weeks), hyperbaric to normobaric (HN; exposed to 36% oxygen at 950 mm Hg for 4 weeks, followed by 21% oxygen at 760 mm Hg for 4 weeks), normobaric to hyperbaric (NH; exposed to 21% oxygen at 760 mm Hg for 4 weeks, followed by 36% oxygen at 950 mm Hg for 4 weeks), and hyperbaric (HH; exposed to 36% oxygen at 950 mm Hg for 8 weeks). RESULTS Blood glucose levels were lower in the HN, NH, and HH groups than in the NN group. Up-regulated mRNA expression levels of peroxisome proliferator-activated receptor-gamma co-activator-1alpha were observed in the soleus muscles of the HN, NH, and HH groups and in the plantaris muscles of the HN and HH groups. The soleus muscles of the NN group contained only type I fibers, whereas those of the HN, NH, and HH groups contained type I, type IIA, and type IIC fibers. An increased percentage of type I fibers and a decreased percentage of type IIB fibers were observed in the plantaris muscles of the NH, HN, and HH groups. CONCLUSIONS Exposure to hyperbaric oxygen reduces high blood glucose levels and improves oxidative capacities in the skeletal muscles of rats with diabetes, and these effects are maintained under normobaric conditions even after exposure to hyperbaric oxygen.

PGC-1α mRNA level and oxidative capacity of the plantaris muscle in rats with metabolic syndrome, hypertension, and type 2 diabetes

We examined the fiber profiles and the mRNA levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β) and of the PPARγ coactivator-1α (PGC-1α) in the plantaris muscles of 15-week-old control (WR), metabolic syndrome (CP), hypertensive (SHR), and type 2 diabetic (GK) rats. The deep regions in the muscles of SHR and GK rats exhibited lower percentages of high-oxidative type I and IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR and CP rats. The surface regions in the muscles of CP, SHR, and GK rats exhibited lower percentages of high-oxidative type IIA fibers and higher percentages of low-oxidative type IIB fibers compared with WR rats. The muscles of SHR and GK rats had lower oxidative enzyme activity compared with WR rats. The muscles of SHR rats had the lowest PPARδ/β mRNA level. In addition, the muscles of SHR and GK rats had lower PGC-1α mRNA level compared with WR and CP rats. We concluded that the plantaris muscles of rats with hypertension and type 2 diabetes have lower oxidative capacity, which is associated with the decreased level of PGC-1α mRNA.

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.

Gene Expression Levels of Heat Shock Proteins in the Soleus and Plantaris Muscles of Rats after Hindlimb Suspension or Spaceflight

Gene expression levels of heat shock proteins (HSPs) in the slow-twitch soleus and fast-twitch plantaris muscles of rats were determined after hindlimb suspension or spaceflight. Male rats were hindlimb-suspended for 14 d or exposed to microgravity for 9 d. The mRNA expression levels of HSP27, HSP70, and HSP84 in the hindlimb-suspended and microgravity-exposed groups were compared with those in the controls. The mRNA expression levels of the 3 HSPs in the soleus muscle under normal conditions were higher compared with those in the plantaris muscle. The mRNA expression levels of the 3 HSPs in the soleus muscle were inhibited by hindlimb suspension and spaceflight. The mRNA expression levels of the 3 HSPs in the plantaris muscle did not change after hindlimb suspension. It is suggested that the mRNA expression levels of the 3 HSPs are regulated by the mechanical and neural activity levels, and therefore the decreased mRNA expression levels of HSPs in the slow-twitch muscle following hindlimb suspension and spaceflight are related to a reduction in the mechanical and neural activity levels.

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.

Effects of Hyperbaric Oxygenation on Blood Pressure Levels of Spontaneously Hypertensive Rats

Five-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to hyperbaric oxygenation with an enhanced atmospheric pressure (950 mmHg) and an increased oxygen concentration (36%) for 6 h per day. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored for 8 weeks of hyperbaric oxygenation period. After 8 weeks of hyperbaric oxygenation, the derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potentials (BAPs) were measured. After 5 weeks of hyperbaric oxygenation, the hyperbaric group of WKY exhibited lower SBP than the age-matched normobaric group, while there were no differences in the DBP between the normobaric and hyperbaric groups. After 3 and 7 weeks of hyperbaric oxygenation, the hyperbaric group of SHR exhibited lower SBP and DBP than the age-matched normobaric group. The hyperbaric groups of both WKY and SHR exhibited lower dROMs than the respective normobaric groups. There were no differences in BAPs between the normobaric and hyperbaric groups of WKY. In contrast, the hyperbaric group of SHR exhibited higher BAPs than the normobaric group. We conclude that the hyperbaric oxygenation conditions used in this study effectively repress hypertension.

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.

Oxygen Concentration-Dependent Oxidative Stress Levels in Rats

Introduction. We determined derivatives of reactive oxygen metabolites (dROMs) as an index of oxidative stress level (oxidant capacity) and biochemical antioxidant potential (BAP) as an index of antioxidant capacity in rats exposed to different oxygen concentrations. Methods. Male Wistar rats were exposed to 14.4%, 20.9%, 35.5%, 39.8%, 62.5%, and 82.2% oxygen at 1 atmosphere absolute for 24 h. Serum levels of dROMs and BAP were examined by using a free radical and antioxidant potential determination device. The morphological characteristics of red blood cells were examined by phase contrast microscopy. Results. There were no differences in the levels of dROMs in rats exposed to 14.4%, 20.9%, and 35.5% oxygen. However, the levels of dROMs increased in the rats exposed to 39.8% and 62.5% oxygen. The levels of dROMs were the highest in the rats exposed to 82.2% oxygen. There were no differences in the levels of BAP with respect to the oxygen concentration. Morphological changes in the red blood cells induced by oxidative attack from reactive oxygen species were observed in the rats exposed to 39.8%, 62.5%, and 82.2% oxygen. Conclusion. Our results suggest that exposure to oxygen concentrations higher than 40% for 24 h induces excessive levels of oxidative stress in rats.

High-fat diet-induced reduction of peroxisome proliferator-activated receptor-γ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome.

Animal models of type 2 diabetes exhibit reduced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.

Effects of hindlimb unloading at early postnatal growth on cell body size in spinal motoneurons innervating soleus muscle of rats

Male Wistar rats were hindlimb‐unloaded from postnatal day 4 to month 3. Some rats were also allowed to reload during 3 months of ambulation recovery. The rats were sacrificed immediately, 1, 2, and 3 months after hindlimb unloading. Numbers, cross‐sectional areas (CSAs), and succinate dehydrogenase (SDH) activities of spinal motoneurons innervating soleus muscle, which were identified by the retrograde neuronal labeling by nuclear yellow, were determined. The numbers, CSAs, and SDH activities of gamma motoneurons (<500 μm2) were not influenced by hindlimb unloading and reloading. The number and SDH activities of alpha motoneurons were not affected by hindlimb unloading and reloading, either. The growth‐related increase of CSA of alpha motoneurons in unloaded group was slightly, but significantly, less than controls. However, the number of small‐sized alpha motoneurons (600–900 μm2) was greater than controls, and large neurons with more than 1300 μm2 CSA were not observed immediately after the 3‐month unloading. These phenomena were gradually recovered and reached the control level at the end of 3‐month ambulation. It is concluded that hindlimb unloading of neonatal rats retards the growth‐related increase in the cell body size of large‐sized alpha motoneurons and that such phenomenon is reversible in response to reloading during ambulation recovery.