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
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
We describe a CMOS multichannel transceiver that transmits and receives 10 Gb/s per channel over balanced copper media. The transceiver consists of two identical 10-Gb/s modules. Each module operates off a single 1.2-V supply and has a single 5-GHz phase-locked loop to supply a reference clock to two transmitter (Tx) channels and two receiver (Rx) channels. To track the input-signal phase, the Rx channel has a clock recovery unit (CRU), which uses a phase-interpolator-based timing generator and digital loop filter. The CRU can adjust the recovered clock phase with a resolution of 1.56 ps. Two sets of two-channel transceiver units were fabricated in 0.11-/spl mu/m CMOS on a single test chip. The transceiver unit size was 1.6 mm /spl times/ 2.6 mm. The Rx sensitivity was 120-mVp-p differential with a 70-ps phase margin for a common-mode voltage ranging from 0.6 to 1.0 V. The evaluated jitter tolerance curve met the OC-192 specification. 相似文献
Repeated batch operation using two fermentors (RBTF) to penicillin fermentation was demonstrated by computer simulation to improve productivity. Three operation modes were compared: chemostat, repeated batch operation using a single fermentor (RBSF) and RBTF; in each case account was made of the lag period before growth. The simulated fermentor performances were assessed on the basis of the penicillin productivity and concentration; the simulation was based on published batch fermentation data. It was shown that RBTF was superior to RBSF and chemostat. The advantage of RBTF increased as the lag period became greater. 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
Vitellogenin of matrotrophic viviparous eelpout (Zoarces elongatus) was purified from estradiol-17 beta (E2) treated immature male sera by gel chromatography and anion exchange chromatography. Isolated vitellogenin has a molecular weight of 540 kDa estimated by gel chromatography. Serum levels of vitellogenin in females were measured during oocyte development and gestation by single radial immunodiffusion. Serum vitellogenin level was low (less than 0.2 mg/ml) during the early vitellogenic period, increased in the late vitellogenic period to a peak level (6.4 +/- 2.1 mg/ml) at the beginning of gestation. After that it rapidly decreased to a low level (0.1 +/- 0.1 mg/ml) during the early gestation period. Levels of vitellogenin remained low throughout the gestation period. Serum E2 levels in females showed increased from 1.3 to 3.0 ng/ml during the late vitellogenic period, and declined to 0.4 ng/ml during the early gestation period. Serum levels of E2 showed good correlation with serum vitellogenin levels, suggesting that the vitellogenin synthesis is controlled by E2 in this species. These results combined with the matrotrophic growth of embryo during gestation suggest that there is a shift in the synthesis of maternal nutritional products for embryos from the yolk to other nutrients. 相似文献