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.     

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.     

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     

Active sites of Cu-ZSM-5 for the decomposition of acrylonitrile

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 (NO_x) 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.     

Applications of computer and numerical analysis techniques in welding research

In recent years, computer technology has made remarkable progress and a computer has become an indispensable tool for both engineers and scientists. In this article, utilization of computers in welding research is briefly summarized. Their use in numerical analysis is particularly discussed and applied to physical phenomena in molten pool, hydrogen diffusion and residual stresses due to welding. A comparison is made between theoretical and experimental results.     

Preoperative thermochemotherapy of oral cancer using magnetic induction hyperthermia (Implant Heating System: IHS)

This study investigated the impact of Difficulty Level and Type of Suggestion upon the durability of posthypnotic suggestion over an 8-week period. Seventy-eight highly susceptible subjects selected by both the Harvard Group Scale of Hypnotic Susceptibility: Form A (HGSHS:A) and Stanford Hypnotic Scale of Susceptibility: Form C (SHSS:C) were assigned to six groups (two levels of Difficulty x three Types of Suggestion). S's were tested for posthypnotic suggestion at 1, 3, 6, and 8 weeks. A 2 x 3 x 4 (Difficulty x Suggestion x Time) factorial ANOVA was conducted, with Time treated as a repeated-measure. The outcome variable at each time was either pass or fail for relevant suggestion. We found a significant Time effect, a significant Difficulty effect, and a significant Time x Difficulty interaction. Fewer subjects passed the difficult suggestions than passed the easy suggestions; fewer passed suggestions at a latter time; and the decay in pass rate was more pronounced for the easy suggestion condition, due largely to the higher initial pass rate. Type of Suggestion was not significant, nor were any of the other interactions. Clinical implications were discussed.     

A CMOS integrated circuit for multichannel multiple-subjectbiotelemetry using bidirectional optical transmissions [weightlessnessin space effects application]

A CMOS integrated circuit for a noninvasive biological-signal telemetry system specified for use in medical and physiological studies of the influence of weightlessness in space is presented. The system can monitor multichannel (4 channels maximum) biological signals from multiple subjects (4 subjects maximum) in real time by using time multiplexing. A key technique so-called synchronized multiple-subject telemetry, to achieve multiple-subject telemetry has been proposed. This technique utilizes bidirectional optical transmissions with direct and scattered infrared lights between an observer and each of the subjects. An experimental CMOS IC to give a small light-weight low-power, and smart telemetry instrument for use on animals has been developed. This IC is for evaluating circuit blocks of the implantable monolithic telemetry instrument. The major circuit blocks include CMOS digital circuits for synchronization, subject selection and time multiplexing, analog circuits for pulse interval modulation, and other blocks such as a CMOS optical pulse receiver and an LED driver. A preliminary experimental multichannel telemetry from two subjects has been performed with the implemented IC chips, and the principal operation of the multiple-subject optical biotelemetry has been demonstrated     

Which vessel is more important in the supercharged flap--artery, vein, or both? An experimental study

The supercharged flap is one which is expected to attain better survival, by anastomosing the distal vessels of the flap to the recipient vessels. An experimental study is reported to determine whether the vessel to be anastomosed should be an artery, a vein, or both. The authors advise anastomosing an artery and a vein, but they believe that arterial inflow is more important than venous drainage.