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.     

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.

     

Prediction of spectral reflectance factor distribution of automotive paint finishes

It is necessary to determine the accurate reflectance of painted surfaces for the review of paint finishes by computer graphics (CG) before actual painting of the exterior color of automobiles, and for quality control during production and inspection processes. We have optimized a method for measuring reflectance by using a statistical technique. We have found that the reflectance of a painted surface is best measured at an incident angle of 60° and at five aspecular angles of 10°, 18°, 28°, 40°, and 90°. Our method makes it possible to accurately reproduce reflection characteristics of paint finishes containing special flake pigments, such as pearl mica. Also it was proved that our method can apply not only to solid and metallic coatings but to all painted surfaces. © 2005 Wiley Periodicals, Inc. Col Res Appl, 30, 275–282, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20125     

Effect of polyurethane surface chemistry on its lipid sorption behavior

The relationships among surface, bulk properties and lipid sorption behaviors of segmented polyurethanes (SPUs) with various polyol soft segments were investigated. The polyols used in this study were poly(ethylene oxide) (PEO), poly(tetramethylene oxide) (PTMO), and poly(dimethylsiloxane) (PDMS). The hard segment of these segmented polyurethanes was composed of 4,4'-diphenylmethane diisocyanate and 1,4-butanediol, present at 50 wt%. X-ray photoelectron spectroscopic (XPS) and dynamic contact angle measurements were carried out in order to analyze the surface chemical structure in the air- and water-equilibrated states. XPS revealed that in the air-equilibrated state, lower surface free energy components were enriched at the air-solid interface, whereas in the water-equilibrated state, higher surface free energy components were enriched at the water-solid interface. The change in environment from air to water induced the surface reorganization in order to minimize interfacial free energy. Lipid sorption behaviors of SPUs were investigated by means of infrared spectroscopy. Even after extensive rinsing of the surface, the amount of lipid present on the SPU surface was more than that calculated on the assumption that a monolayer covers the SPU surface. Therefore, the lipid was not only adsorbed on the surface of SPU but absorbed into SPU. The SPU with hydrophilic PEO sorbed larger amount of phospholipid compared with that with hydrophobic polyol such as PTMO and PDMS. Also, the competitive sorption behaviors of phospholipid and cholesterol from their mixed liposome solution were studied. The ratio of sorbed cholesterol to phospholipid increased with an increase in surface hydrophobicity owing to the hydrophobic nature of cholesterol.     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.     

Inter- and intra-molecular ionic interactions of polyampholyte: Carboxymethyl-2-diethylaminoethylcellulose

Carboxymethyl-2-diethylaminoethylcellulose (CM-DEAE cellulose) was prepared by etherification of carboxymethylcellulose with diethylaminoethyl chloride in a NaOH solution. The behaviour of CM-DEAE cellulose in aqueous solution was studied by viscosity and GPC measurements. The degree of substitution (DS) and existing states of DEAE substituents were examined by the use of proton NMR, and those of the CM substituents were observed with FT-IR. The results reveal that the reduced viscosity and apparent molecular size of CM-DEAE cellulose vary with the concentration of sodium chloride and changes in pH and DS. These phenomena can be explained in terms of inter- and intra-molecular ionic interactions.     

Damage tolerance of glass mat/epoxy laminates hybridized with flexible resin under static and impact loading

This study deals with the impact property and damage tolerance of matrix hybrid composite laminates with different laminate constitution. The matrix hybrid composite laminates consisted of the laminae with a conventional epoxy resin and the laminae with a flexible epoxy resin modified from the conventional resin to avoid the interlaminar delamination. The impact energy absorption ratio greatly depended on the matrix resin placed at the impact face. The energy absorption was almost constant if the conventional resin was placed at the impact surface layer, while it increased exponentially with the increasing fraction of the flexible resin if the flexible resin was placed at the impact face. The impact energy was absorbed by the damage development and propagation in the laminate with conventional resin laminae as the impacted face, while it was absorbed by both the recoverable deformation of the flexible resin and the damage propagation in the laminate with flexible resin laminae as the impacted face.     

The oxidation properties of fourth generation single-crystal nickel-based superalloys

The fourth-generation nickel-based single-crystal superalloys, which contain large amounts of refractory metals for strengthening and platinum group metals for topologically close-packed phase prevention, show excellent high-temperature strength. However, these alloying elements seem to decrease high-temperature oxidation resistance. In this study, nickel-based superalloys with various amounts of tantalum, rhenium, and ruthenium were examined in isothermal and cyclic exposures at 1,100°C to investigate the effect on the oxide growth rate and resistance to scale spallation. Ruthenium and rhenium were found to degrade the oxidation resistance by the vaporization of their oxide. Tantalum-rich oxide in the spinel layer acts to stabilize ruthenium and rhenium oxide in the scale. The addition of hafnium and yttrium is effective in improving the oxidation resistance of ruthenium-containing nickel-based superalloys.     

Influence of third monomer on the crystal phase transition behavior of ethylene-tetrafluoroethylene copolymer

Crystal phase transition between the low- and high-temperature phases has been investigated for ethylene (E)-tetrafluoroethylene (TFE) alternating copolymer (ETFE) containing the third monomeric species by the temperature dependent measurements of wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) and differential scanning calorimetry. Nonafluoro-1-hexene (NFH) and hexafluoropropylene (HFP) were chosen as the third monomers, where they are different in the side-branch length, -(CF₂)₃CF₃ and -CF₃, respectively. In the case of E/TFE/NFH copolymer (ET-C4F9), the crystal phase transition temperature of the original ETFE two-components copolymer was not very much affected by the existence of NFH in the range of NFH content from 0.7 to 3 mol%. Contrarily, the crystal phase transition temperature of E/TFE/HFP copolymer (ET-CF3) was found to decrease drastically with increasing HFP content. The melting temperature and the higher-order structure were also affected sensitively depending on the HFP content. This difference in phase transition behavior between ET-C4F9 and ET-CF3 copolymers is reasonably interpreted as follows: the short side groups (-CF₃) of HFP monomeric unit are included in the crystal lattice of E/TFE chains and the unit cell is expanded gradually with an increment of the HFP content, resulting in the decrease in phase transition point because of easier thermal motion of the chains. On the other hand, the long side groups [-(CF₂)₃CF₃] of NFH monomeric units are excluded out of the crystal lattice and located on the lamellar surfaces or in the amorphous region and do not affect very much the phase transition temperature even when the NFH content is increased. In association with such a change in crystal structure, the long period of stacked lamellar structure was found to decrease remarkably in the case of NFH, whereas it does not change very much for HFP, consistent with the interpretation of the above-mentioned WAXD data.