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排序方式: 共有762条查询结果,搜索用时 15 毫秒
1.
Hideaki Kaneto Tomohiko Kimura Atsushi Obata Masashi Shimoda Kohei Kaku 《International journal of molecular sciences》2021,22(5)
While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history. 相似文献
2.
Mitsuo Miyazawa Tomohiko Takahashi Kazuki Sakata Isao Horibe 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2008,83(7):1006-1011
BACKGROUND: The biotransformation of sesquiterpenoids, which are a large class of naturally occurring compounds, using microorganisms as a biocatalyst to produce useful novel organic compounds was investigated. The biotransformation of sesquiterpenoids, (+)‐aromadendrene ( 1 ), (−)‐alloaromadendrene ( 2 ) and (+)‐ledene ( 3 ) has been investigated using Aspergillus wentii as a biocatalyst. Results: Compound 1 was converted to (−)‐(10S,11S)‐10,13,14‐trihydroxyaromadendrane ( 4 ). Compound 2 was converted to (+)‐(1S,11S)‐1,13‐dihydroxyaromadendrene ( 5 ) and (−)‐5,11‐epoxycadin‐1(10)‐en‐14‐ol ( 6 ). Compound 3 was converted to compound 6 , (+)‐(10R,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 7 ) and (+)‐(10S,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 8 ). The structure of the metabolic products has been elucidated on the basis of their spectral data. CONCLUSION: Compound 1 gave only one product that was hydroxylated at C‐10, C‐13 and C‐14. By contrast, compounds 2 and 3 gave a number of products, one of which was common. The differences in oxidation of 1–3 are due to the configuration of the C‐1 position. Compounds 4–8 were new compounds. Copyright © 2008 Society of Chemical Industry 相似文献
3.
En-Hai Sun Yong-Ho Choa Tohru Sekino Tomohiko Adachi Koichi Niihara 《Materials Research Innovations》2002,6(3):105-111
Cordierite/ZrO2 composites with 5 to 25 wt% ZrO2 were fabricated by conventional powder mixing and pressureless sintering method. Their densification behavior, microstructure,
mechanical and thermal properties were studied. By dispersing 25 wt% (9.57 vol%) ZrO2, densified cordierite/ZrO2 composite with a relative density of 98.5% was obtained at an optimum sintering condition of 1440 °C and 2 h. ZrO2 particles were homogenously dispersed within matrix grains and at the grain boundaries. The intragranular particles were
finer than 100 nm and the intergranular particles were coarser. Both fracture strength and toughness could be enhanced more
than two times higher, compare to those of monolithic cordierite, by dispersing 25 wt% ZrO2 into the cordierite matrix. The toughening mechanism in the present composites was mainly attributed to martensitic transformation
due to ZrO2 dispersion.
Electronic Publication 相似文献
4.
In order to investigate the influence of puffer volume V/sub P/ and operating force to dielectric performance of GCB at current interruption, we calculated the prospective dielectric withstand voltage V/sub W/ between arcing contacts. The withstand voltage was calculated by the electric field strength appeared on arcing contacts and the allowable electric field strength E/sub W//sup */ of hot gas due to thermal puffer action. We could clarify that large initial puffer volume V/sub P/ can increase withstand voltage V/sub W/ at current breaking point and also that an optimum point exists in operating force F. For example, it was found that in case of the operating force of 1000 kgf, the puffer volume V/sub P/ of 1.2 liter would be best choice in the interrupting condition of i=50 kA and arcing time of 1.35 cycle. 相似文献
5.
Y Nakajima O Mikami M Yoshioka Y Motoi T Ito Y Ishikawa M Fuse K Nakano K Yasukawa 《Canadian Metallurgical Quarterly》1997,62(3):297-298
The presence of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) activities was determined in milk and serum of cows with naturally occurring coliform mastitis (CFM). TNF-alpha was detected in the sera from 26 of 32 cows with CFM. TNF-alpha levels were higher in the sera than in the milk. IL-6 was high in the sera of surviving CFM animals, but was low in animals that died and in healthy controls. Furthermore, the mean level of IL-6 was 20-fold higher in the milk than in the sera of mastitic cows. The level of IL-6 in the serum was correlated to that in the milk in individual animals. The presence of IL-6 and TNF-alpha in the sera appears to relate to severe clinical condition of CFM, in the milk whereas they may play a role in generating inflammation of the mammary gland. 相似文献
6.
Structural changes in the Brill transitions of Nylon 10/10 and its model compounds have been investigated by carrying out the temperature-dependent measurements of X-ray diffraction and infrared spectra along with the DSC measurement. The crystal structure at room temperature was found to be the so-called α form with the all-trans zigzag methylene segments. When the samples were heated, the infrared progression bands of the methylene segments, which are sensitive to the length of all-trans segmental parts, were found to change their spectral patterns in the transition temperature region: the progression bands decreased in intensity and disappeared above the transition region. At the same time several new bands were observed to appear, which were found to correspond to the progression bands of (CH2)7-(CH2)5trans-zigzag segments. These spectral changes indicate that the methylene segments were conformationally disordered by an invasion of some gauche bonds and as a result the effective length of trans-zigzag segments became shorter. This conformational disordering was found to occur more remarkably in the methylene segment of NH-(CH2)10-NH part than the CO-(CH2)8-CO part. At the same time the infrared bands of amide groups, in particular the bands sensitive to the twisting angles about the CH2-amide bonds were found to show the remarkable change, indicating the local conformational change from planar-zigzag to twisted form in the CH2-amide moiety. The frequency shift of amide A band (NH stretching mode) indicated a weakening of intermolecular hydrogen bonds, which however, did not disappear up to the melting region. From these data combined with the X-ray diffraction data, the structural disordering in the Brill transition phenomena was deduced concretely. 相似文献
7.
A Miyazawa H Inoue T Yoshioka T Horikoshi K Yanagisawa M Umeda K Inoue 《Canadian Metallurgical Quarterly》1992,59(4):1547-1554
Understanding the topographical relationships between phosphatidylserine (PS) and protein kinase C (PKC) within neurons can provide clues about the mechanism of translocation and activation of PKC. For this purpose we applied monoclonal antibodies (Abs) of PS and PKC to sections of developing rat cerebellum. The anti-PKC Ab immunohistochemical pattern showed homogeneous staining of Purkinje cells over various postnatal ages, whereas the anti-PS Ab staining showed a heterogeneous localization over these ages. Purkinje cells did not stain well between postnatal day 14 (PND 14) and PND 21, suggesting that the PS was lost from the membrane during preparation of the sections during this period. These data imply that interactions between PS and PKC vary in Purkinje cells during postnatal development. 相似文献
8.
9.
M Miyata E Fukaya T Takagi K Watanabe H Saito M Ito R Yoshioka Y Kazuta Y Yusa A Irisawa Y Sato T Nishimaki H Kumakawa R Kasukawa 《Canadian Metallurgical Quarterly》1998,37(12):1058-1063
Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion. 相似文献
10.
N Yoshioka 《Canadian Metallurgical Quarterly》1995,47(11):1255-1260
This paper shows the value of Doppler ultrasound of the uterine blood flow in predicting the effect of GnRHa on myoma uteri. Thirty-eight patients with myoma uteri were divided into two groups by Doppler ultrasound before treatment: a group with positive arterial blood flow in or around the myoma nodule, and another group with negative arterial blood flow. Histological examinations which were performed in thirty patients demonstrated that the myoma in the negative blood flow group showed higher hyalinization with poor vascularization. In fifteen patients treated with GnRHa (Buserelin 900 micrograms/day), a significant increase (p < 0.01) in the resistance index of the uterine arteries was induced and suppressed the serum estradiol concentration in all cases during GnRHa therapy. The size of the myoma nodules also decreased in all 6 patients in the positive blood flow group, but in only 3 of the 9 patients in the negative blood flow group during GnRHa therapy. These results indicated that Doppler assessments of the arterial blood flow in myoma would be useful in predicting the effect of GnRHa on myoma uteri. 相似文献