Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozin

BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulation of energy metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear. METHODS: We investigated the factors associated with the beneficial effects of dapagliflozin, a SGLT2 inhibitor, in the liver after confirming its glucose-lowering and weight loss effects using an obesity and diabetes mouse model. We also performed clinical study of patients with type 2 diabetes to explore candidate biomarkers that reflect the beneficial action of dapagliflozin in the liver. FINDINGS: In animal study, dapagliflozin induced autophagy in the liver (LC3-II to LC3-I expression ratio: P < 0·05 vs. control), and valine and leucine levels were increased in plasma (P < 0·01 vs. control) as well as in liver (P < 0·05 vs. control). Thus, increased plasma valine and leucine levels are potential biomarkers for improved liver metabolism. Clinical study found that valine and leucine levels were markedly higher in patients treated with dapagliflozin (valine: P < 0·05 vs. control, leucine: P < 0·01 vs. control) than those not treated after one week intervention. INTERPRETATION: Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine and leucine levels may reflect its metabolic effect. FUNDING: AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), Novo Nordisk Pharma Ltd., and Japan Foundation for Applied Enzymology, and MSD Life Science Foundation International

Low-power display system enabled by combining oxide semiconductor and neural network technologies

An oxide semiconductor (OS)-based field effect transistor (OSFET) exhibits the advantage of having an extremely low off-state current; moreover, the OSFET displays an off-state current that is ten orders of magnitude lower than that of a CMOS-FET [1]. Recently, numerous applications that harness this feature have been reported [2]. For instance, charge leakage from a data retention node of a pixel significantly decreases when the display incorporates OSFETs in its pixel circuit (OS display) [3, 4]. This minimizes degradation in the image quality when the displayed image is static despite using lower refresh rates. Consequently, the consumed power of the display driver circuit can be reduced by a large margin. This driving method is termed idling stop (IDS) driving. The OSFET’s low-leakage can also effectively enable a type of ULSICs that we term OS-large-scale integrated circuits (OSLSI) [5, 6]. Please click Additional Files below to see the full abstract

2017～2019年度 関西大学研究拠点形成支援経費研究成果報告書

目次・研究成果の概要・2-1　工藤 宏人・宮前 翼・上田 正人・村山 憲弘・林 順一 "ノーリア骨格をテンプレートとした空孔内に水酸基を有する架橋化合物の合成とそれらの金属イオン包接性能" ネットワークポリマー論文集 vol.41, No.2, 65 - 71 (2020).・2-2　Mitsuaki Matsuoka, Kaho Yokoyama, Kohei Okura, Norihiro Murayama, Masato Ueda, Makio Naito " Synthesis of Geopolymers from Mechanically Activated Coal Fly Ash and Improvement of Their Mechanical Properties" Minerals 9, 791- 801 (2019).・2-3　Daisuke Shimoyama, Ryo Sekiya, Hiroto Kudo, Takeharu Haino, "Feet-to-Feet Connected Trisresorcinarenes" Organic Letters 22, 352 - 356 (2019).・2-4　Masato Ueda, Masahiko Ikeda, Shigeo Mori, Kenji Doi, Hisashi Kitagaki, Shuntaro Terauchi "Mechanical Properties of Additively Manufactured Porous Titanium with Sub-Millimetre Structural Units" Materials Transactions Vol.60, No.9, 1792 - 1798 (2019).・2-5　五十井 浩平・白杉 文香・松岡 光昭・林 順一・村山 憲弘 "種々のMg-Fe系複合酸化物を用いた希薄水溶液中のホウ素およびヒ素の除去" 環境資源工学 66, 29 - 35 (2019).・2-6　Toru Maruyama, Mitsuyoshi Tamaki, Keisuke Nakamura, Gou Nakamura "EFFECT OF MOLTEN METAL TEMPERATURE ON MOLD FILLING IN EVAPORATIVE PATTERN CASTING" International Journal of Metalcasting 13, 611–617 (2019).・2-7　Ryuta Saito, Toru Maruyama, Toshiki Nakamura, Hitoshi Yanagitani, Takahiro Sakai, Kouji Nakamoto "Influence of Tellurium Addition to Spheroidal Graphite Cast Iron on the Number of Graphite Particles" International Journal of Metalcasting Vol.13, 3, 571-577 (2018).・2-8　Masato Ueda, Rika Yamaguchi, Chika Fujita, Masahiko Ikeda "Control of Cell Adhesion on Titanium Dioxide by Light Irradiation" Materials Science Forum Vol.941, 2507 - 2512 (2018).・2-9　Hiroto Kudo, Mari Fukunaga, Kohei Shiotsuki, Hiroya Takeda, Hiroki Yamamoto, Takahiro Kozawa, Takeo Watanabe "Synthesis of hyperbranched polyacetals containing C-(4-t-butylbenz)calix[4]resorcinarene: Resist properties for extreme ultraviolet (EUV) lithography" Reactive and Functional Polymers 131, 361 - 367 (2018).・2-10　大隈 修・前 一廣・林 順一 "直接液化による豪州ビクトリア褐炭の高度利用 : 改新BCLプロセスによる化学原料の生産" Journal of the Japan Institute of Energy 98, 17 - 26 (2019).・2-11　Issei Suzuki, Ayako Kakinuma, Masato Ueda, Takahisa Omata "Flux growth of β-NaGaO₂ single crystals" Journal of Crystal Growth 504, 26 -30 (2018).・2-12　上田 正人、坂本 貴則、池田 勝彦 "電気抵抗率の精密測定による純チタンの組織評価" 環境資源工学 65, 74 -76 (2018).・2-13　Satoshi Imasaka, Hiroyasu Ishii, Jun\u27ichi Hayashi, Sadao Araki, Hideki Yamamoto "Synthesis of CHA-type titanosilicate zeolites using titanium oxide as Ti source and evaluation of their physicochemical properties" Microporous and Mesoporous Materials 273, 243-248 (2019).・2-14　Hiroto Kudo, Shizuya Ohori, Hiroya Takeda, Hiroki Ogawa, Takeo Watanbe, Hiroki Yamamoto, Takahiro Kozawa "Synthesis and Property of Tannic Acid Derivatives and Their Application for Extreme Ultraviolet Laser Lithography System" Journal of Photopolymer Science and Technology Vol.31, 221 - 225 (2018).・2-15　Hiroto Kudo, Tsubasa Miyamae, Kouta Kitagawa, Kohei Isoi, Norihiro Murayama, Jun\u27ichi Hayashi " Synthesis and Metal-Complexation Ability of Cross-Linking Materials Containing Noria-Templated Cavities with Pendant Carboxylic Acid Groups" Chemistry Select 3, 2223 - 2228 (2018).・2-16　上田 正人、池田 勝彦、土井 研児、 森 重雄、北垣 壽、寺内 俊太郎、関 あずさ "骨部分置換用ポーラスチタン : ポリグリコール酸 : 炭酸カルシウム複合体の開発" 高分子論文集 Vol.75, No.1, 69 - 74 (2018).・2-17　Alexandru C Sonoc, Jacob Jeswiet, Norihiro Murayama, Junji Shibata "A study of the application of Donnan dialysis to the recycling of lithium ion batteries" Hydrometallurgy 175, 133 - 143 (2018).2-3は、著作権の関係により非公開としております。2-8は、著作権の関係により非公開としております。2-9は、著作権の関係により非公開としております。2-10は、著作権の関係により非公開としております。2-11は、著作権の関係により非公開としております。2-16は、著作権の関係により非公開としております

The Effect of White Rice and White Bread as Staple Foods on Gut Microbiota and Host Metabolism

The purpose of this study was to examine the influence of two kinds of major Japanese staple foods, white rice and white bread, on gut microbiota against the background in which participants eat common side dishes. Seven healthy subjects completed the dietary intervention with two 1-week test periods with a 1-week wash-out period in cross-over design (UMIN registration UMIN000023142). White bread or white rice and 21 frozen prepared side dishes were consumed during the test periods. At baseline and at the end of each period, fasting blood samples, breath samples, and fecal samples were collected. For fecal samples, 16S rRNA gene sequencing was used to analyze the gut microbiota. After the bread period, the abundance of fecal Bifidobacterium genus (19.2 &plusmn; 14.5 vs. 6.2 &plusmn; 6.6 (%), p = 0.03), fasting glucagon-like peptide 1 (GLP-1) (13.6 &plusmn; 2.0 vs. 10.5 &plusmn; 2.9 (pg/mL), p = 0.03), and breath hydrogen (23.4 &plusmn; 9.9 vs. 8.2 &plusmn; 5.5 (ppm), p = 0.02) were significantly higher than those of after the rice period. Plasma SCFAs also tended to be higher after the bread period. White bread contains more dietary fiber than refined short grain rice. These findings suggest that indigestible carbohydrate intake from short grain rice as a staple food may be smaller than that of white bread

Generating Mechanism of Catalytic Effect for Hydrogen Absorption/Desorption Reactions in NaAlH4–TiCl3

The hydrogen desorption and absorption reactions of the complex metal hydride NaAlH4 are disproportionation processes, and the kinetics can be improved by adding a few mol% of Ti compounds, although the catalytic mechanism, including the location and state of Ti, remains unknown. In this study, we aimed to reveal the generating mechanism of catalytic Al–Ti alloy in NaAlH4 with TiCl3 using quantum multiprobe techniques such as neutron diffraction (ND), synchrotron X-ray diffraction (XRD), anomalous X-ray scattering (AXS), and X-ray absorption fine structure (XAFS). Rietveld refinements of the ND and XRD, profiles before the first desorption of NaAlD(H)4–0.02TiCl3 showed that Al in NaAlD(H)4 was partially substituted by Ti. On the other hand, Ti was not present in NaAlH4, and Al–Ti nanoparticles were detected in the XRD profile after the first re-absorption. This was consistent with the AXS and XAFS results. It is suggested that the substitution promotes the formation of a highly dispersed nanosized Al–Ti alloy during the first desorption process and that the effectiveness of TiCl3 as an additive can be attributed to the dispersion of Ti

Single Molecule Dynamics at a Mechanically Controllable Break Junction in Solution at Room Temperature

The in situ observation of geometrical and electronic structural dynamics of a single molecule junction is critically important in order to further progress in molecular electronics. Observations of single molecular junctions are difficult, however, because of sensitivity limits. Here, we report surface-enhanced Raman scattering (SERS) of a single 4,4′-bipyridine molecule under conditions of in situ current flow in a nanogap, by using nano-fabricated, mechanically controllable break junction (MCBJ) electrodes. When adsorbed at room temperature on metal nanoelectrodes in solution to form a single molecule junction, statistical analysis showed that nontotally symmetric <i>b</i>₁ and <i>b</i>₂ modes of 4,4′-bipyridine were strongly enhanced relative to observations of the same modes in solid or aqueous solutions. Significant changes in SERS intensity, energy (wavenumber), and selectivity of Raman vibrational bands that are coincident with current fluctuations provide information on distinct states of electronic and geometrical structure of the single molecule junction, even under large thermal fluctuations occurring at room temperature. We observed the dynamics of 4,4′-bipyridine motion between vertical and tilting configurations in the Au nanogap via <i>b</i>₁ and <i>b</i>₂ mode switching. A slight increase in the tilting angle of the molecule was also observed by noting the increase in the energies of Raman modes and the decrease in conductance of the molecular junction