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
Radiophotoluminescence phenomena have been widely investigated on various types of materials for dosimetry applications. We report that an aluminoborosilicate glass containing 0.005 mol% copper exhibits intense photoluminescence in the visible region induced by X-ray and γ-ray irradiation. The luminescence is assigned to the 3d94s1 → 3d10 transition of Cu+. The proportionality of the intensity of the induced photoluminescence to the irradiation dose was confirmed up to 0.5 kGy using 60Co γ-ray irradiation. Based on the spectroscopic results, a potential mechanism was proposed for the enhancement of the photoluminescence. The exposure to the ionizing radiation generates electron-hole pairs in the glass, and the electrons are subsequently captured by the Cu2+ ions, which are converted to Cu+ and emit the luminescence. For the glass containing 0.01 mol% copper, the pronounced enhancement of the photoluminescence was not observed because the reverse reaction, ie, the capture of the holes by the Cu+ ions, becomes prominent. The photoluminescence induced by the irradiation was stably observed for the glasses kept at room temperature and even for the glasses heat-treated at 150°C. However, the induced photoluminescence could be eliminated by the heat treatment at a temperature at 500°C, and the glass returned to the initial pre-irradiation state. The Cu-doped aluminoborosilicate glass is a potential candidate for use in dosimetry applications. 相似文献
Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria. 相似文献
A lotus-type porous carbon steel with cylindrical pores was fabricated by the continuous zone melting method in a pressurized
mixture of hydrogen and helium gases. The porosity increases with increasing partial pressure of the hydrogen gas, while the
pore diameter remains almost constant, independent of the pressure. The ultimate tensile strength of the specimen with cylindrical
pores parallel to the tensile direction is lower than the estimated value, assuming that the strength is decreased in proportion
to the decrease of the cross-sectional area of the specimen, while the yield strength is higher than the estimated value.
The compressive yield strength is also higher than the estimated value. The increase in yield strength is considered to be
due to precipitation strengthening. The tensile strength is increased by quenching and tempering, while the elongation decreases.
Such mechanical properties are discussed in terms of the microstructural analysis. 相似文献
Summary
The potato phosphorylase-catalyzed polymerization of α-D-glucose-1-phosphate (G-1-P) onto poly[styrene-block-(4-vinylbenzyl maltohexaoside)] (1) was performed at the molar ratios of [G-l-P]0 and [maltohexaose]0 of 35, 80, and 250. The product was found to be soluble in dimethyl sulfoxide, which was a good solvent for amylose, and
showed the complex-formation with iodine, indicating that the product was assignable to poly[styrene-block-(styrene-graft-amylose)] (2). The quantitative analysis of the liberated phosphoric acid gave the average degree of polymerization o f the glucose unit
(n) as 27, 5 1, and 180 for 2-I, 2-II, and 2-III, respectively.
Received: 29 November 2002/Accepted: 22 December 2002
Correspondence to Toyoji Kakuchi 相似文献
The catalytic decomposition of acrylonitrile (AN) over Cu-ZSM-5 prepared with various Cu loadings was investigated. AN conversion, during which the nitrogen atoms in AN were mainly converted to N2, increased as Cu loading increased. N2 selectivities as high as 90–95% were attained. X-ray diffraction measurements (XRD) and temperature-programmed reduction by H2 (H2-TPR) showed the existence of bulk CuO in Cu-ZSM-5 with a Cu loading of 6.4 wt% and the existence of highly dispersed CuO in Cu-ZSM-5 with a Cu loading of 3.3 wt%. Electron spin resonance measurements revealed that Cu-ZSM-5 contains three forms of isolated Cu2+ ions (square-planar, square-pyramidal, and distorted square-pyramidal). The H2-TPR results suggested that in Cu-ZSM-5 with a Cu loading of 2.9 wt% and below, Cu+ existed even after oxidizing pretreatment. The activity of AN decomposition over Cu/SiO2 suggested that CuO could form N2, but, independent of the CuO dispersion, nitrogen oxides (NOx) were formed above 350 °C. Cu+ and the square-pyramidal and distorted square-pyramidal forms of Cu2+ showed low activity for AN decomposition. Temperature-programmed desorption of NH3 suggested that N2 formation from NH3 proceeded on Cu2+, resulting in the formation of Cu+. The Cu+ ions were oxidized to Cu2+ at around 300 °C. Thus, high N2 selectivity over Cu-ZSM-5 with a wide range of temperature was probably attained by the reaction over the square-planar Cu2+, which can be reversibly reduced and oxidized. 相似文献
Dopaminergic blocking agents have been known to suppress intracranial self-stimulation, but whether the suppression results from a reduction in the rewarding value of stimulation or from motor deficits has remained controversial. We have resolved this controversy by developing an operant technique minimally dependent on motor activity; rats were trained to perform a bar-holding response for 3s or to produce hippocampal theta waves for 3s when the bar was retracted. Decamethonium bromide (a muscle relaxant) reduced bar holding without affecting theta production for brain stimulation. Pimozide (a dopaminergic blocking-agent) reduced both bar holding and theta production for stimulation, though rats were still capable of making the theta response at a rate comparable to the preinjection rate. Dopaminergic blocking at low doses reduces the rewarding value of brain stimulation at the level of the lateral hypothalamus. The method described in this report has wide applicability. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
The establishment time of gas-liquid two-phase flows in a cylindrical bath agitated by bottom gas injection through a central
single-hole bottom nozzle was investigated. Because the turbulence intensity in the bath was comparable to or larger than
the unity, the conventional definition of the flow establishment time based on the history of mean velocity was not suitable
for the present case. In fact, it was difficult to determine the flow establishment time based on the well-known 90 or 99
pct criterion for the mean velocity. Accordingly, two methods of determining the flow establishment time by focusing on the
turbulence components instead of the mean velocity components were proposed. Velocity measurements were made with a two-channel
laser Doppler velocimeter. The flow establishment time was correlated as a function of gas flow rate. Close agreement was
obtained by the two methods. 相似文献
A simple fabrication technology for delta-doped MOSFETs, named post-low-energy implanting selective epitaxy (PLISE) is presented. The PLISE technology needs no additional photo-lithography mask, deposition step or etching step even for CMOS devices. The only additional step is growing undoped epitaxial channel layers by UHV-CVD after the channel implantation. With this technology, delta-doped NMOSFETs with 0.1-μm gate length were successfully fabricated. By optimizing the epi-layer thickness and the channel doping level, short-channel effects are suppressed enough to achieve 0.1-μm gate length. Moreover, the junction capacitance at zero bias is reduced by 50% 相似文献