Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

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.     

Dynamic probe of ZnTe(110) surface by scanning tunneling microscopy

The reconstructed surface structure of the II–VI semiconductor ZnTe (110), which is a promising material in the research field of semiconductor spintronics, was studied by scanning tunneling microscopy/spectroscopy (STM/STS). First, the surface states formed by reconstruction by the charge transfer of dangling bond electrons from cationic Zn to anionic Te atoms, which are similar to those of IV and III–V semiconductors, were confirmed in real space. Secondly, oscillation in tunneling current between binary states, which is considered to reflect a conformational change in the topmost Zn–Te structure between the reconstructed and bulk-like ideal structures, was directly observed by STM. Third, using the technique of charge injection, a surface atomic structure was successfully fabricated, suggesting the possibility of atomic-scale manipulation of this widely applicable surface of ZnTe.     

Radiophotoluminescence phenomenon in copper-doped aluminoborosilicate glass

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.     

Distribution of carbon contamination in MgAl2O4 spinel occurring during spark-plasma-sintering (SPS) processing: I – Effect of heating rate and post-annealing

Carbon contamination from the carbon paper/dies during spark-plasma-sintering (SPS) processing was examined in the MgAl₂O₄ spinel. The carbon contamination sensitively changes with the heating rate during the SPS processing. At the high heating rate of 100 °C/min, the carbon contamination having organized structures occurred over almost the entire area from the surface to deep inside the SPSed spinel disk. In contrast, at the slow heating rate of 10 °C/min, the carbon contamination having disordered structures occurred only around the surface area. The carbon phases transform into high pressure CO/CO₂ gases by post-annealing in air and lead to pore formation along the grain junctions. The pore formation significantly occurs at the high heating rate due to the large amount of the contaminant carbon phases. This suggests that if once the carbon contamination was formed in the materials, it is very difficult to remove the carbon phases from the materials.     

Matrix influence on the piezoelectric properties of piezoelectric ceramic/polymer composite exhibiting particle alignment

This study was addressed to the influence of an electric field strength applied at fabrication process and matrix properties, such as the dielectric constant and the Young's modulus, on “pseudo‐1‐3 piezoelectric ceramic/polymer composite” in order to further enhance the piezoelectricity of that. The pseudo‐1‐3 piezoelectric ceramic/polymer composite consists of linearly ordered piezoelectric ceramic particles in polymer material. Silicone gel, silicone rubber, urethane rubber, and poly‐methyl‐methacrylate, which exhibit different dielectric constants and Young's modulus, were used as matrices to evaluate the matrix influence. The piezoelectricity of the pseudo‐1‐3 piezoelectric ceramic/polymer composite was evaluated using the piezoelectric strain constant d₃₃. The d₃₃ is one of the indices of the piezoelectric properties for piezoelectric materials. As a result, it was confirmed that d₃₃ of the pseudo‐1‐3 piezoelectric ceramic/polymer composite increased with the increase of the electric filed strength applied at fabrication process, though, it reached a constant value at a certain strength value. Further it was confirmed that dielectric constant of the matrix had a small influence on d₃₃ of the pseudo‐1‐3 piezoelectric ceramic/polymer composite, however, in case of matrix of lower Young's modulus, d₃₃ was increase. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41817.     

Cover Image,Volume 69, Issue 3

The cover image is based on the Mini‐Review Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications by Takeshi Endo et al., https://doi.org/10.1002/pi.5952 . Cover image © Takeshi Endo Images.

     

Glycoconjugated polymer 6. Synthesis of poly[styrene-<Emphasis Type="Italic">block</Emphasis>-(styrene-<Emphasis Type="Italic">graft</Emphasis>-amylose)] via potato phosphorylase-catalyzed polymerization

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     

Serum vanadium levels in chronic hemodialysis patients

Serum vanadium, aluminum, silicon and beta 2-microglobulin levels as well as the red cell count, hemoglobin and systolic blood pressure were simultaneously measured in 80 chronic hemodialysis patients. The serum vanadium level was positively correlated with the serum levels of aluminum, silicon and beta 2-microglobulin as well as the systolic blood pressure, and was inversely correlated with the red cell count and hemoglobin. The mean serum vanadium level was 18.4 +/- 7.6 ng/ml before hemodialysis and decreased to 13.0 +/- 5.30 ng/ml at the completion of dialysis. The dialysate vanadium level increased from 0.4 +/- 0.2 (inflow) to 1.0 +/- 0.4 ng/ml (outflow). It was concluded that vanadium was transferred from blood to dialysate when purified water was used in the preparation of the dialysate.