Search PubMed⌕ Search

Biomedical subjects

Hiroshi Shibata

Publications and source records attributed to Hiroshi Shibata.

15 recordsLinked to original sources

Insulin recruits GLUT4 from distinct compartments via distinct traffic pathways with differential microtubule dependence in rat adipocytes.

In the present study, we investigated the physiological significance of the microtubules in the subcellular localization and trafficking of GLUT4 in rat primary adipocytes. Morphological and biochemical analyses revealed a dose- and time-dependent disruption of the microtubules by treatment with nocodazole. With nearly complete disruption of the microtubules, the insulin-stimulated glucose transport activity was inhibited by 55%. This inhibition was concomitant with a comparable inhibition of GLUT4 translocation measured by the subcellular fractionation and the cell-surface GLUT4 labeling by trypsin cleavage. In addition, the time-course of insulin stimulation of the glucose transport activity was significantly delayed by microtubule disruption (t(1/2) were 7 and 2.3 min in nocodazole-treated and control cells, respectively), while the rate of GLUT4 endocytosis was little affected. The impaired insulin-stimulated glucose transport activity was not fully restored to the level in control cells by blocking GLUT4 endocytosis, suggesting that the inhibition was due to the existence of a microtubule-dependent subpopulation in the insulin-responsive GLUT4 pool. On the other hand, nocodazole partially inhibited insulin-induced translocation of the insulin-regulated aminopeptidase and the vesicle-associated membrane protein (VAMP)-2 without affecting GLUT1 and VAMP-3. In electrically permeabilized adipocytes, the insulin-stimulated glucose transport was inhibited by 40% by disruption of the microtubules whereas that stimulated with GTP gamma S was not affected. Intriguingly, the two reagents stimulated glucose transport to the comparable level by disruption of the microtubules. These data suggest that insulin recruits GLUT4 to the plasma membrane from at least two distinct intracellular compartments via distinct traffic routes with differential microtubule dependence in rat primary adipocytes.

3-O-Methylglucose↗

Novel antioxidative metabolites in rat liver with ingested sesamin.

Sesamin, a major lignan in sesame oil, is known to have many biological activities, especially protective effects against oxidative damage in the liver. As sesamin itself has no antioxidative properties in vitro, to elucidate the mechanism of its antioxidative effects, the reaction products of sesamin in rat liver homogenate were analyzed. The methylenedioxyphenyl moiety in the structure of sesamin was shown to be changed into a dihydrophenyl (catechol) moiety. The enzymatic reaction products in vitro were identified as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, which showed strong radical scavenging activities; the latter was a novel compound. The same metabolites were found as glucuronic acid and/or sulfic acid conjugates in substantial amounts in rat bile after oral administration of sesamin. It is suggested that sesamin is a prodrug and the metabolites containing the catechol moieties in their structures are responsible for the protective effects of sesamin against oxidative damage in the liver.

Animals↗

Cellsorba.

Cellsorba is a leukocyte removal filter developed by Asahi Medical Co., which adsorbs white blood cells through the perfusion of peripheral blood by means of simple extracorporeal circulation. Leukocytapheresis (LCAP) therapy using the Cellsorba column has been reported to show therapeutic effects for many autoimmune related and inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, neurologic disease, and so on. At present, Cellsorba is listed as a medical device covered by the Japanese national health insurance system for the treatment of active ulcerative colitis (UC) in Japan, and contributes to the improvement of quality of life in many UC patients. This paper reviews the use of Cellsorba and introduces several reports on therapeutic results.

Arthritis, Rheumatoid↗

Hypolipemic effect of Cyclocarya paliurus (Batal) Iljinskaja in lipid-loaded mice.

We investigated the inhibitory effect of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) extract on postprandial hyperlipemia in mice. A single oral administration of C. paliurus extract (250 mg/kg) suppressed an increase in plasma triacylgycerol (TG) levels when fed with 5 ml/kg of lard and olive oil. The inhibition rates were 28.6% and 24.1%, respectively, but free fatty acid (FFA) levels in plasma were not significantly affected as compared with control group mice. In addition, C. paliurus extract showed inhibitory activity toward pancreatic lipase, a key enzyme of dietary TG absorption, with an IC(50) of 9.1 microg/ml in vitro. Our results suggested that the hypolipemic action of C. paliurus extract was probably interrelated with suppression of the activity of digestive lipase, and as a result, the blood lipid level was reduced.

Animals↗

Inhibitory effect of oolong tea on the oxidative state of low density lipoprotein (LDL).

In the present study, we investigated the anti-oxidant activity of oolong tea in an oxidation model using human low-density lipoprotein (LDL). Oolong tea suppressed the oxidation of LDL induced by 2-2'-azobis 4-methoxy-2,4-dimethyvaleronitrile (V70) in a dose-dependent manner, that is, it prolonged the lag time to 114.3%, 138% and 199.9% as compared with the control group at 0.5 microg/ml, 1.0 microg/ml, and 2.5 microg/ml, respectively. We also determined the scavenging effect of oolong tea on active oxygen radicals using the electron spin resonance (ESR) technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. The intensity of the ESR signals for the DMPO-OOH adduct formed by the hypoxanthine/xanthine oxidase reaction system with DMPO decreased in the presence of oolong tea. The IC(50) of oolong tea was 19.9 microg/ml. These findings suggested that oolong tea has beneficial effects on health related to its anti-oxidative action.

Antioxidants↗

Hypoglycemic action of Cyclocarya paliurus (Batal.) Iljinskaja in normal and diabetic mice.

This study examined the hypoglycaemic activity of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) in ICR mice by oral glucose tolerance testing. The blood glucose level was significantly lower in the C. paliurus extract treatment group than in the control group after animals were given sucrose. This difference was not observed following the administration of glucose. We demonstrated that the chronological change in the level of blood glucose in genetically hyperglycemic obese KK-Ay mice is significantly lower when C. paliurus extract is administered daily for three weeks. An in vitro study showed that C. paliurus inhibits alpha-glucosidase, a disaccharide-degrading enzyme in the small intestinal mucosa, leading to a decrease in the absorption of glucose into the blood and a subsequent lowering of the blood glucose level.

Animals↗

[Stress-buffering effects of coping strategies among caregivers for impaired Japanese elderly].

This study examines stress-buffering effects of coping strategies among caregivers for Japanese impaired elderly. Eight hundred thirty-two valid responses obtained from primary caregivers of impaired persons aged 65 years old and over living in the community were analyzed. A path model was constructed with physical disability and cognitive impairment of the elderly as the primary stressor, caregiving captivity as the secondary stressor, followed by burnout. Main and interaction effects of five coping strategies were examined by regression analysis with interaction terms between the primary stressor, the secondary stressor, and five coping strategies. Four main effects of coping strategies were found: "Diversion" decreased caregiving captivity; "Keeping their own pace," "Positive acceptance of caregiving role," and "Diversion" decreased burnout. Two buffering effects were found: "Diversion" decreased caregiving captivity only at low level of Activities of Daily Living (ADL) impairment; "Keeping their own pace" buffered the detrimental effects of caregiving captivity for burnout.

Activities of Daily Living↗

Influence of caffeine ingestion on autonomic nervous activity during endurance exercise in humans.

The effects of caffeine ingestion on the activities of the autonomic nervous system (ANS) during endurance exercise at low intensity were investigated using a power spectrum analysis of heart rate variability. Placebo or caffeine (300 mg) capsules were randomly administered to the subjects. Each subject ingested the samples 2 h before cycling on an ergometer for 30 min at an intensity corresponding to 40%-50% of his ventilatory threshold. The electrocardiogram, blood pressure (BP) and gas exchange parameters were monitored during rest and exercise. The results indicated that there were no significant differences in heart rate and systolic blood pressure between the trials. The spectrum integrated values of the low frequency power and total power components in the caffeine trial were significantly greater than in the placebo trial during exercise, which implied that activities of the ANS were augmented by caffeine. Caffeine also induced enhanced lipid oxidation as shown by the significantly lower respiratory gas exchange ratio and increases in diastolic blood pressure during exercise. The results shed some light upon the relationship between the activity of the ANS, energy metabolism and BP. In conclusion, the results suggest that caffeinated beverages have a potential to be useful supplements to the prescription of exercise for individuals who experience a depressed activity of the ANS. The results also suggest that the experiment protocol used in this study is a sensitive and noninvasive method for evaluating the effects of various foods and nutrients on the activity of the ANS.

Adult↗

T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation in smokers: possible gene-environmental interaction.

Effects of smoking on white matter lesions, such as lacunar infarction and leukoaraiosis, are still controversial. We hypothesized that the endothelial NO synthase (eNOS) genotype was a modulating factor for the effect of smoking on cerebral circulation. We took a cross-sectional population from the participants of a health examination to study the effects of smoking and a single-nucleotide polymorphism in the eNOS gene, T-786C. Smokers and nonsmokers were defined as having a smoking index (cigarettes per day times years) of >/=200 and 0, respectively. One hundred sixty-six male nonsmokers and 344 male smokers were recruited. Cerebral blood flow was measured by the (133)Xe inhalation method. Genotyping of T-786C was performed by using a newly developed allele-specific polymerase chain reaction. Smokers were exposed to greater oxidative stress, as estimated by urinary F(2)-isoprostane excretion. In smokers, CC homozygotes of T-786C showed a significant decrease of cerebral blood flow (56.6+/-13.3, 57.6+/-11.5, and 44.0+/-7.2 mL/min per 100 g tissue for TT, TC, and CC, respectively; P=0.03 by ANOVA) and a significant increase of cerebrovascular resistance, whereas the eNOS genotype did not affect these parameters in nonsmokers. This result indicated that the eNOS genotype could modify cerebrovascular circulation in a general population by potentiating the adverse effect of smoking.

Analysis of Variance↗

Effects of oolong tea on metabolism of plasma fat in mice under restraint stress.

We investigated the effects of oolong tea on the basic metabolism of plasma lipids in mice under restraint stress. When a lipid emulsion (Intralipid 20%; a lipid emulsion containing 20% soybean oil) was injected intravenously into mice, the restraint stress prolonged the half-life (T 1/2) of elimination for plasma triglyceride (TG) from 28.7 to 55.5 min. The elimination rate per minute was 48.2% in stressed mice with the rate in starved control mice as 100%. Therefore, TG metabolism was disrupted by the stress, and the use of TG as an energy source decreased. We found that the metabolism of lipids significantly response to the restrained stress in the present study. Plasma TG was 515.9 +/- 29.9mg/dl 35min after Intralipid administration in control stressed mice, 478.7 +/- 26.7 mg/dl in the stressed group given caffeine 100 mg/kg of body weight, and 418.3 +/- 18.4 mg/dl in the stressed group given 1,000 mg/kg oolong tea, an improvement by 7.2% and 18.9%, respectively, with the value for the untreated control group. The intake of oolong tea alleviated the stress-induced decrease in the rate of blood lipid metabolism; this effect may have arisen from some non-specific stress-relieving property of the tea or from acceleration of lipid metabolism by properties of polyphenols, etc. in tea. Oolong tea had anti-stress effects on plasma TG metabolism, and the effects did not depend on caffeine.

Animals↗

Study of the causes of higher mortality rates from chronic liver diseases in Tokushima Prefecture.

Mortality rates from chronic liver diseases (CLD) such as liver cirrhosis and hepatocellular carcinoma have been reported to be higher in Tokushima prefecture, although its causes remain unclear. To clarify the causes of CLD in Tokushima prefecture, we evaluated the positive rates of HBs antigen and anti-HCV antibody and the mortality rates from CLD in patients with liver diseases and blood donors after dividing the entire Tokushima prefecture into 8 district boundaries of health centers. In addition, to evaluate the causes of the higher frequency of CLD and the relationship between the development of CLD and viruses, medical examinations were performed in 2 mountain villages in Tokushima prefecture where the drift of population was limited and the mortality rates from CLD differed from each other. As a result, it was found that HCV infection was the major cause of the higher mortality rates from CLD in Tokushima prefecture. Although there were marked regional differences in the mortality rates from CLD, they were mainly due to different rates of HCV infection.

Adult↗

Longitudinal changes in higher-level functional capacity of an older population living in a Japanese urban community.

This study examined the present state and longitudinal changes in higher-level functional capacity in a Japanese urban community. Persons aged 65-84 years living in a suburb of central Tokyo participated in a baseline survey held in 1991 (n = 814) and followed-up for 8 years. Outcome measures were disabilities in: instrumental self-maintenance (IADL), the intellectual activity scale (intellectual activity) and the social role scale (social role), as measured by subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-index of competence). At baseline among the three subscales, both older men and women had the highest prevalence of disability in social role, followed in turn by intellectual activity and IADL disability. The 8-year longitudinal survey on subjects who had no initial disability (229 men and 235 women) in all three subscales of TMIG-index of competence demonstrated that they were most likely to lose social role function with advancing age, followed in turn by intellectual activity and IADL. The Cox proportional hazard model analysis for all 814 participants revealed that baseline level of social role and intellectual activity significantly predicted the new onset of IADL disability during the 8-year follow-up period even after controlling for gender, age, and chronic medical conditions. In summary, disability in social role and intellectual activity do not only likely precede IADL disability, but also predict significantly the future onset of IADL disability in a Japanese urban community older population.

Activities of Daily Living↗