Yamauchi 2022 Sci Rep

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.

» https://pubmed.ncbi.nlm.nih.gov/35697838/

Yamauchi Yuki, Nakamura Akinobu, Yokota Takashi, Takahashi Kiyohiko, Kawata Shinichiro, Tsuchida Kazuhisa, Omori Kazuno, Nomoto Hiroshi, Kameda Hiraku, Cho Yong Kyu, Anzai Toshihisa, Tanaka Shinya, Terauchi Yasuo, Miyoshi Hideaki, Atsumi Tatsuya (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. • Keywords: diabetes, islet, mitochondria, pancreas, reactive oxygen species

• 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