Tauroursodeoxycholic Acid Protect Against Type 2 Diabetes Through Suppression of Pancreatic TBP-2 and Preservation of Thioredoxin Activity

Ratan Hossain; Khokon Kumar Dutta; Aitijjo Bhowmick; Probir Kumar  Banerjee; Md. Tofazzal Hossain; Choyan  Biswas; Mst Tamanna  Yasmin; Mst Muslima  Khatun

doi:10.71193/jmct.20260012

Authors

Ratan Hossain Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0003-1193-3957
Khokon Kumar Dutta Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0003-2453-1279
Aitijjo Bhowmick Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0005-9633-8536
Probir Kumar Banerjee Department of Gastroenterology, Gopalganj Medical College & Hospital, Goplaganj 8100, Bangladesh Author https://orcid.org/0009-0002-6692-4444
Md. Tofazzal Hossain Department of Statistics, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0000-0002-8281-6059
Choyan Biswas Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0000-6496-9900
Mst Tamanna Yasmin Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0002-4052-838X
Mst Muslima Khatun Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh Author https://orcid.org/0009-0004-1801-1928

DOI:

https://doi.org/10.71193/jmct.20260012

Keywords:

Tauroursodeoxycholic acid (TUDCA), Ursodeoxycholic acid (UDCA), Thioredoxin-interacting protein (TXNIP/TBP-2), mitochondrial shuttling, type 2 diabetes

Abstract

Endoplasmic reticulum (ER) stress contributes to the development of type 2 diabetes mellitus (T2DM) by inducing thioredoxin-interacting protein (TXNIP/TBP-2), a key mediator of oxidative stress, mitochondrial dysfunction, and pancreatic β-cell injury. This study investigated whether tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA), two bile acids with ER stress–reducing properties, protect against T2DM through modulation of the pancreatic TBP-2/thioredoxin pathway. Combined TUDCA and UDCA supplementation markedly reduced diabetes incidence in high-fat diet (HFD)– and streptozotocin-induced diabetic rats (34% vs. 75% in untreated animals) and attenuated body weight gain. Mechanistically, rats protected from diabetes exhibited significantly lower pancreatic TBP-2 expression and reduced mitochondrial accumulation of TBP-2 compared with untreated diabetic rats. Preservation of both total and reduced thioredoxin activity was observed in supplemented animals, and thioredoxin activity was inversely associated with pancreatic and mitochondrial TBP-2 levels. These findings indicate that suppression of TBP-2 expression and inhibition of its mitochondrial translocation are closely linked to improved pancreatic redox homeostasis and resistance to diabetes development. In conclusion, TUDCA and UDCA protect against diabetogenesis by limiting TBP-2–mediated oxidative stress and preserving thioredoxin function, identifying the TBP-2/thioredoxin axis as a potential therapeutic target for T2DM.

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Author Biographies

Ratan Hossain, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Graduate Student, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh
Khokon Kumar Dutta, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Associate Professor and Chairman, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh
Probir Kumar Banerjee, Department of Gastroenterology, Gopalganj Medical College & Hospital, Goplaganj 8100, Bangladesh

Associate Professor, Department of Gastroenterology, Gopalganj Medical College & Hospital, Gopalganj 8100, Bangladesh
Md. Tofazzal Hossain, Department of Statistics, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Associate Professor, Department of Statistics, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh
Choyan Biswas, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Graduate Student, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh
Mst Tamanna Yasmin, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Graduate Student, Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh
Mst Muslima Khatun, Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

Graduate Student, Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj 8105, Bangladesh

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