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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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 |
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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 |
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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. |
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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 |
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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 |
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ACADEMIC PRESS INC ELSEVIER SCIENCE |
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2024 |
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http://eprints.um.edu.my/44220/ https://doi.org/10.1016/j.bbrc.2023.149392 |
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1805881137007951872 |
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13.211869 |