The incidence of dementia is higher in diabetic patients, but no effective treatment has been developed. This study showed that rat bone marrow mesenchymal stem cells (BM-MSCs) can improve the ...cognitive impairments of STZ-diabetic mice by repairing damaged neurons and astrocytes. The Morris water maze test demonstrated that cognitive impairments induced by diabetes were significantly improved by intravenous injection of BM-MSCs. In the CA1 region of the hippocampus, degeneration of neurons and astrocytes, as well as synaptic loss, were prominent in diabetes, and BM-MSC treatment successfully normalized them. Since a limited number of donor BM-MSCs was observed in the brain parenchyma, we hypothesized that humoral factors, especially exosomes released from BM-MSCs, act on damaged neurons and astrocytes. To investigate the effectiveness of exosomes for treatment of diabetes-induced cognitive impairment, exosomes were purified from the culture media and injected intracerebroventricularly into diabetic mice. Recovery of cognitive impairment and histological abnormalities similar to that seen with BM-MSC injection was found following exosome treatment. Use of fluorescence-labeled exosomes demonstrated that injected exosomes were internalized into astrocytes and neurons; these subsequently reversed the dysfunction. The present results indicate that exosomes derived from BM-MSCs might be a promising therapeutic tool for diabetes-induced cognitive impairment.
The figure is available here: thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Figures Citation: Amitani H, Asakawa A, Cheng K, Amitani M, Kaimoto K, Nakano M, et ...al. (2013) Correction: Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle.
1 Department of Medicine and Clinical Science, Graduate School of Medicine, 2 Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, and 3 ...Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Submitted 15 September 2006
; accepted in final form 19 November 2006
5'-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1- - D -ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the 1 - and 2 -isoforms of AMPK, with a corresponding increase in the rate of 3- O -methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3- O -methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.
contraction; glycogen synthase; glycogen phosphorylase; epitrochlearis muscle; glycolysis
Address for reprint requests and other correspondence: T. Hayashi, Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto Univ., Yoshida-nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan (e-mail: tatsuya{at}kuhp.kyoto-u.ac.jp )
The anti-suck-back ability of five new high-speed air turbine handpiece models was evaluated in this study. First, suck-back pressure with water displacement within a glass tube was measured. Next, ...under three different conditions, how many on-off times it takes before fluorescent stains became visible on a piece of gauze at the exhaust vent was counted and the presence of fluorescent stains on the exhaust vents itself was examined. As a result, the water height for each part of one handpiece, the TWINPOWER TURBINE PAR-4HX-O, was below 0 mm. Except for under full emersion, this model, the TWINPOWER TURBINE PAR-4HX-O, did not have any visible fluorescence penetration to the exhaust vent even after 500 on-off switches under fume/mist conditions. Conversely, the other handpieces (Ti-Max X700L, T1 CONTROL, SYNEA TA-98CLED, GENTLE silence LUX 8000B) showed suck-back. In conclusion, the first mentioned new turbine handpiece, the TWINPOWER TURBINE PAR-4HX-O, had a possibility of no suck-back by itself. However, full immersion of the whole head of the handpiece which is not completely sealed must be avoided to prevent liquid intake.
The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder ...Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.
Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive ...normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.