Yamauchi 2022 Sci Rep: Difference between revisions
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Revision as of 14:08, 15 June 2022
Yamauchi Y, Nakamura A, Yokota T, Takahashi K, Kawata S, Tsuchida K, Omori K, Nomoto H, Kameda H, Cho KY, Anzai T, Tanaka S, Terauchi Y, Miyoshi H, Atsumi T (2022) Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function. Sci Rep 12: 9740. |
ยป https://pubmed.ncbi.nlm.nih.gov/35697838/
Yuki Yamauchi, Akinobu Nakamura, Takashi Yokota, Kiyohiko Takahashi, Shinichiro Kawata, Kazuhisa Tsuchida, Kazuno Omori, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Toshihisa Anzai, Shinya Tanaka, Yasuo Terauchi, Hideaki Miyoshi, Tatsuya Atsumi (2022) Sci Rep
Abstract: We aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation were performed using isolated islets. Immunohistochemistry and electron microscopic analysis were performed using pancreatic tissues. Metabolites extracted from the islets were measured by capillary electrophoresis mass spectrometry. The expression of genes involved in the tricarboxylic acid (TCA) cycle and electron transport chain was upregulated by luseogliflozin. Luseogliflozin improved the mitochondrial complex II-linked oxidative phosphorylation capacity and reduced ROS generation. Mitochondrial morphology was normally maintained by luseogliflozin. Luseogliflozin increased NK6 homeobox 1 (NKX6.1) expression and TCA cycle metabolites. Relief of glucotoxicity by luseogliflozin may involve lower mitochondrial ROS generation and an improvement in complex II-linked mitochondrial respiration. Reducing ROS generation through preventing complex II damage likely increases NKX6.1 expression and ameliorate glucose metabolism in the TCA cycle, contributing to the protection of pancreatic beta-cells. Protection of complex II in pancreatic beta-cells represents a novel therapeutic target for type 2 diabetes. โข Keywords: diabetes, islet, mitochondria, pancreas, reactive oxygen species
โข O2k-Network Lab: JP Sapporo Yokota T
Labels: MiParea: Respiration
Pathology: Diabetes
Organism: Mouse Tissue;cell: Islet cell;pancreas;thymus
Enzyme: Complex I, Complex II;succinate dehydrogenase Regulation: ADP, Redox state, Substrate Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k, O2k-Fluorometer
JP, 2022-12