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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.
3.
Tatsuro Tanaka Yoshifumi Maeda Shinji Yamamoto Toru Iwao 《Electrical Engineering in Japan》2019,207(1):15-23
The arc welding has been used in various welding methods because it is inexpensive and high in strength after welding. However, it is a problem that accidents such as collapse of the bridge occur because of the welding defects. The welding of low cost and high productivity is required without the welding defects. The pulsed TIG welding is inexpensive and capable of high‐quality welding. The electromagnetic force contributing to penetration changes because the transient response of arc temperature and iron vapor generated from anode occurs. However, the analysis of pulsed TIG welding with metal vapor has been elucidated only metal vapor concentration near anode with transient phenomenon and heat flux. Thus, the theoretical elucidation of penetration depth with control factor has not been researched. In this paper, the contribution of metal vapor mass at the periphery part of pulsed arc to the electromagnetic force in the weld pool is elucidated. As a result, the iron vapor mass at periphery part decreased with increasing the frequency. The iron vapor was stagnated at axial center within one cycle. The electromagnetic force to the penetration depth direction in weld pool increased at axial center. Therefore, the metal vapor mass at periphery part plays an important role for the electromagnetic force increment at axial center. 相似文献
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The In-site of Ba2In2O5 with Brownmillerite structure was partially substituted for Ce4+ ions in order to examine the doping effect on the order-disorder transition. Ba2In2 – x
Ce
x
O5 + x/2 (x = 0.1, 0.2, 0.3, 0.5, 1.0, and 1.5) were prepared by solid state reaction. X-Ray diffraction analyses of these powder samples demonstrated that Ba2In2 – x
Ce
x
O5 + x/2 (x = 0.1 and 0.2) possesses Brownmillerite structure. With increasing content of Ce4+ ion the crystal system of Ba2In2 – x
Ce
x
O5 + x/2 (x = 0.3, 0.5, and 1.0) changed to cubic perovskite structure above the order-disorder transition temperature of Ba2In2O5. Arrhenius plots of the electrical conductivities of Ba2In2 – x
Ce
x
O5 + x/2 (x = 0.2, 0.3, and 1.0) exhibited no discontinuity. These compounds had high transference numbers of oxide ion above 973 k. 相似文献
6.
H Asahara K Fujisawa T Kobata T Hasunuma T Maeda M Asanuma N Ogawa H Inoue T Sumida K Nishioka 《Canadian Metallurgical Quarterly》1997,40(5):912-918
Green fluorescent protein (GFP) is increasingly being used in plant biology from the cellular level to whole plant level. At the cellular level, GFP is being used as an in vivo reporter to assess frequency of transient and stable transformation. GFP has also proven to be an invaluable tool in monitoring trafficking and subcellular localization of protein. At the organ level and up, many exciting applications are rapidly emerging. The development of brighter GFP mutants with more robust folding properties has enabled better macroscopic visualization of GFP in whole leaves and plants. One interesting example has been the use of GFP to monitor virus movement in and among whole plants. GFP is also emerging as a powerful tool to monitor transgene movement and transgenic plants in the field. In a proof-of-concept study, tobacco was transformed with a modified version of the GFP gene controlled by a constitutive (35S) promoter. GFP expression in progeny plants ranged from 0% to 0.5%, and approximately 0.1% GFP was the minimal amount needed for unambiguous macroscopic detection. GFP is the first truly in vivo reporter system useful in whole plants, and we project its usefulness will increase even further as better forms of GFP genes become available. 相似文献
7.
We show here that the internucleosomal DNA fragmentation, which is a biochemical hallmark of apoptosis, was induced in a cell density-dependent manner in primary culture of adult rat hepatocytes. This DNA fragmentation could be suppressed by a gene expression inhibitor, indicating the active nature of this process. Moreover, the viability changes in high and low cell density cultures showed a tendency corresponding with the incidence of the DNA fragmentation in them. These results suggest that in hepatocytes there may be a cell density-dependent apoptosis mechanism. In this report, we also show that heparin could suppress this DNA fragmentation with high specificity, and the cell death to some extent. 相似文献
8.
Yamaoka M. Shinozaki Y. Maeda N. Shimazaki Y. Kato K. Shimada S. Yanagisawa K. Osada K. 《Solid-State Circuits, IEEE Journal of》2005,40(1):186-194
An on-chip 1-Mb SRAM suitable for embedding in the application processor used in mobile cellular phones was developed. This SRAM supports three operating modes - high-speed active mode, low-leakage low-speed active mode, and standby mode - and uses a subdivisional power-line control (SPC) scheme. The combination of three operating modes and the SPC scheme realizes low-power operation under actual usage conditions. It operates at 300 MHz, with leakage of 25 /spl mu/A/Mb in standby mode, and 50 /spl mu/A/Mb at the low-leakage active mode. This SRAM also uses a self-bias write scheme that decreases of minimum operating voltage by about 100 mV. 相似文献
9.
10.
Heterogeneous curable compositions of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisphenol A diglycidyl ether (BADG) systems were prepared by merely mixing these components at room temperature. Stability at room temperature and cure properties at high temperature of the compositions were investigated for evaluating their applicability as one part adhesive. It was found that the systems containing Mg were generally more stable than those containing Ca. Similarly, at 150°C the Ca-containing systems showed generally shorter gelation time than the Mg-containing ones, due to the fact that the Ca salt dissolves more rapidly and enters into the addition reaction with the anhydride, leading to the faster appearance of the catalytic activities of the Ca carboxylate group. Among the various combinations of components, the metal salt–succinic anhydride (SA)–BADG systems were stable at room temperature for more than 6 months and rapidly cured at high temperature, showing excellent adhesive properties. This result indicates that the SA-containing systems should be of interest in applications to one part adhesives. 相似文献