Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
Document Type
Article
Publication Date
1-29-2024
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.
Keywords
Diabetes, 8-cells, TXNIP, Shiga-Y6, Akita mice
Divisions
fac_med
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]
Publication Title
Biochemical and Biophysical Research Communications
Volume
694
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Publisher Location
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA