Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes

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 qu...

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Main Authors: Aldoghachi, Asraa Faris, Yanagisawa, Daijiro, Arrozi, Aslina Pahrudin, Bakar, Zulzikry Hafiz Abu, Taguchi, Hiroyasu, Ishigaki, Shinsuke, Morino, Katsutaro, Tooyama, Ikuo
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Published: ACADEMIC PRESS INC ELSEVIER SCIENCE 2024
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Online Access:http://eprints.um.edu.my/44220/
https://doi.org/10.1016/j.bbrc.2023.149392
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spelling my.um.eprints.442202024-06-25T04:53:15Z http://eprints.um.edu.my/44220/ Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes Aldoghachi, Asraa Faris Yanagisawa, Daijiro Arrozi, Aslina Pahrudin Bakar, Zulzikry Hafiz Abu Taguchi, Hiroyasu Ishigaki, Shinsuke Morino, Katsutaro Tooyama, Ikuo R Medicine (General) RM Therapeutics. Pharmacology 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. ACADEMIC PRESS INC ELSEVIER SCIENCE 2024-01-29 Article PeerReviewed 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 <https://doi.org/10.1016/j.bbrc.2023.149392>. https://doi.org/10.1016/j.bbrc.2023.149392 10.1016/j.bbrc.2023.149392
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine (General)
RM Therapeutics. Pharmacology
spellingShingle R Medicine (General)
RM Therapeutics. Pharmacology
Aldoghachi, Asraa Faris
Yanagisawa, Daijiro
Arrozi, Aslina Pahrudin
Bakar, Zulzikry Hafiz Abu
Taguchi, Hiroyasu
Ishigaki, Shinsuke
Morino, Katsutaro
Tooyama, Ikuo
Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
description 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.
format Article
author Aldoghachi, Asraa Faris
Yanagisawa, Daijiro
Arrozi, Aslina Pahrudin
Bakar, Zulzikry Hafiz Abu
Taguchi, Hiroyasu
Ishigaki, Shinsuke
Morino, Katsutaro
Tooyama, Ikuo
author_facet Aldoghachi, Asraa Faris
Yanagisawa, Daijiro
Arrozi, Aslina Pahrudin
Bakar, Zulzikry Hafiz Abu
Taguchi, Hiroyasu
Ishigaki, Shinsuke
Morino, Katsutaro
Tooyama, Ikuo
author_sort Aldoghachi, Asraa Faris
title Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
title_short Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
title_full Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
title_fullStr Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
title_full_unstemmed Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes
title_sort fluorinated curcumin derivative (shiga-y6) modulates the level of thioredoxin-interacting protein (txnip) in a mouse model of diabetes
publisher ACADEMIC PRESS INC ELSEVIER SCIENCE
publishDate 2024
url http://eprints.um.edu.my/44220/
https://doi.org/10.1016/j.bbrc.2023.149392
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