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.     

Galvanic cell measurements on supersaturated activities of oxygen in Fe-Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) melts

Using a mullite (3Al₂O₃ · 2SiO₂)-tube and ZrO₂-9 mol pct MgO-plug type solid electrolyte galvanic cells, the activities of supersaturated oxygen in Fe-0.0017 to 0.41 mass pct Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) alloys were measured as a function of total Al or M contents at 1873 K in an alumina crucible. Based on these results, the effects of alloying elements on the supersaturated oxygen activity with respect to alumina precipitation were studied. In the Fe-Al-M (M=C, Te, Mn, Cr, and Si) alloys, the supersaturated oxygen activities for a given Al level approach the equilibrium values with increasing contents of alloying elements. However, the oxygen activities for a given Al level are still supersaturated in the Fe-Al-M (M=Ti, Zr, and Ce) alloys even in the presence of considerable amounts of the alloying elements.     

Intramolecular triplet energy migration in poly(2-vinylnaphthalene) and poly(naphthylalkyl methacrylate)s in solid solution: Effects of side chain length

Summary The effect of side chain length on intramolecular triplet energy migration of naphthalene containing polymers was investigated by a delayed fluorescence (DF) spectroscopy for the solid solution of the polymers. The degree of triplet energy migration depends strongly on whether the chromophores are directly attached to the main chain or not.     

Transient analysis of an advanced static var compensator using quad-series voltage-source PAM inverters

This paper deals with an advanced static Var compensator (ASVC) using quad-series voltage-source PAM inverters. The ASVC consists of four three-phase voltage-source inverters with a common dc capacitor and four three-phase transformers, each primary winding of which is connected in series with each other. Each inverter outputs a square-wave voltage, while the synthesized output voltage of the ASVC has a 24-step wave shape. This results not only in a great reduction of harmonic currents and dc voltage ripples but also in fewer switching and snubbing losses. In this paper, transient analysis is performed with the focus on the response of reactive power and the resonance between the dc capacitor and ac reactors. Experimental results obtained from a small-rated laboratory model of 10 kVA are also shown to verify analytical results based on the p-q transformation. The analytical results help in the design of system parameters such as the capacity of the dc capacitor and feedback gains.     

Tissue compatibility of polylactic acids in the skeletal site

This study was undertaken to examine the osseous tissue compatibility of polylactic acid (PLA) with properties of bioabsorbability and plasticity. Two kinds of granular PLA with different molecular weight (PLA-H: 28 000 MW, PLA-L: 10 600 MW) were implanted into rat tibiae and light microscopic sections were prepared at 1, 2, 4, 8, 16, and 24 weeks following surgery. The tissue compatibility of the PLAs was compared with that of hydroxyapatite (HAP) which is a non-absorbable biocompatible material. After implantation, both PLAs were gradually absorbed and replaced by marrow tissue at 24 weeks. PLA-H degraded slower than PLA-L. New bone formation was observed around each PLA by 4 weeks, and a vast amount of bone deposited on PLA-H at 16 weeks. Phagocytic reactions to the PLAs were noted, however, severe inflammation was not seen. HAP was not absorbed and bone surrounded it throughout the experiment. These results indicate good tissue compatibility of PLA as a bioabsorbable material at the skeletal site.     

Synthesis and applications of fluoroalkyl end-capped cooligomers having fullerene and mixed fullerenes in the main chain

Fluoroalkanoyl peroxides reacted with FULLERENES [fullerene (C₆₀) and commercially available fullerenes (Nanom Mix^TR and Nanom Black^TR)] and radical polymerizable comonomers such as acrylic acid, N,N-dimethylacrylamide, N-(1,1-dimethyl-3-oxobutyl)acrylamide, and acryloylmorpholine to afford fluoroalkyl end-capped cooligomers having FULLERENES in the main chain under very mild conditions. Fluoroalkyl end-capped Nanom Mix and Nanom Black cooligomers thus obtained were found to exhibit a similar solubility to that of the corresponding fluoroalkyl end-capped cooligomers having fullerene in the main chain. These fluorinated FULLERENES cooligomers were found to form the nanometer size-controlled self-assembled cooligomeric aggregates in aqueous solutions. These fluoroalkyl end-capped FULLERENES cooligomers were more effective for solubilizing fullerene, Nanom Mix and Nanom Black into water, compared to those of the corresponding fluoroalkyl end-capped homooligomers having no FULLERENES in the main chain. Fluoroalkyl end-capped fullerene- and Nanom Mix-acrylic acid cooligomers were found to exhibit fluorescence spectra related to fullerene and Nanom Mix in cooligomers, respectively, in aqueous solutions. Additionally, these fluorinated fullerene- and Nanom Mix-acrylic acid cooligomers were able to increase chemiluminescence intensity related to luminol, effectively, compared to the corresponding fluorinated acrylic acid homooligomers.