Aldoghachi, Asraa Faris and Yanagisawa, Daijiro and Arrozi, Aslina Pahrudin and Bakar, Zulzikry Hafiz Abu and Taguchi, Hiroyasu and Ishigaki, Shinsuke and Morino, Katsutaro and Tooyama, Ikuo (2024) Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes. Biochemical and Biophysical Research Communications, 694. ISSN 1090-2104, DOI https://doi.org/10.1016/j.bbrc.2023.149392.
Full text not available from this repository.Abstract
Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of 8-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/ kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of 8-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both a- to 8-cell ratio and the number of apoptotic 8-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic 8-cells apoptosis.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) [JP20K20588], Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) [JP23H03722], Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) [JP22K08650], Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) [JP22K07370] |
| Uncontrolled Keywords: | Diabetes; 8-cells; TXNIP; Shiga-Y6; Akita mice |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 25 Jun 2024 04:53 |
| Last Modified: | 25 Jun 2024 04:53 |
| URI: | http://eprints.um.edu.my/id/eprint/44220 |
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