TUDCA receptors and their role on pancreatic beta cells

Rosa, Lucas Rodolfo de Oliveira; Vettorazzi, Jean Franciesco; Zangerolamo, Lucas; Carneiro, Everardo M.; Barbosa, Helena Cristina de Lima

doi:10.1016/j.pbiomolbio.2021.09.003

Cited by 6 publications

(9 citation statements)

References 52 publications

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“…It is necessary to keep in mind that TUDCA can exert its actions through other receptors, such as Takeda G-protein receptor 5 (TGR5), α5β1 integrin, and farnesoid X receptor (FXR) 41 . The action of TUDCA through FXR seems to be controversial within the literature.…”

Section: Discussionmentioning

confidence: 99%

“…The action of TUDCA through FXR seems to be controversial within the literature. Some studies point out that FXR has a low affinity for TUDCA (and its precursor, UDCA), due to hydrophilic nature of these bile acids 41 . However, in a presence of bile acid transporter, such as Na + -taurocholate co-transporting polypeptide (NTCP) in hepatocytes, TUDCA can enter cells and bind to the nuclear receptor FRX 42 .…”

Section: Discussionmentioning

confidence: 99%

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The bile acid TUDCA reduces age-related hyperinsulinemia in mice

Zangerolamo

Carvalho

Barssotti

et al. 2022

Sci Rep

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Aging is associated with glucose metabolism disturbances, such as insulin resistance and hyperinsulinemia, which contribute to the increased prevalence of type 2 diabetes (T2D) and its complications in the elderly population. In this sense, some bile acids have emerged as new therapeutic targets to treat TD2, as well as associated metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic acid (TUDCA) improves glucose homeostasis in T2D, obesity, and Alzheimer's disease mice model. However, its effects in aged mice have not been explored yet. Here, we evaluated the actions of TUDCA upon glucose-insulin homeostasis in aged C57BL/6 male mice (18-month-old) treated with 300 mg/kg of TUDCA or its vehicle. TUDCA attenuated hyperinsulinemia and improved glucose homeostasis in aged mice, by enhancing liver insulin-degrading enzyme (IDE) expression and insulin clearance. Furthermore, the improvement in glucose-insulin homeostasis in these mice was accompanied by a reduction in adiposity, associated with adipocyte hypertrophy, and lipids accumulation in the liver. TUDCA-treated aged mice also displayed increased energy expenditure and metabolic flexibility, as well as a better cognitive ability. Taken together, our data highlight TUDCA as an interesting target for the attenuation of age-related hyperinsulinemia and its deleterious effects on metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The bile acid TUDCA reduces age-related hyperinsulinemia in mice

Zangerolamo

Carvalho

Barssotti

et al. 2022

Sci Rep

Self Cite

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“…Several studies, in vitro, and in vivo, are currently unravelling potential S1P pathways in pancreatic cancer development and how these pathways may contribute to resistant phenotypes [192][193][194]. One such pathway being extensively studied is conjugated bile acid (tauroursodeoxycholic acid (TUDCA))'s activation of S1PR2-ERK1/2/AKT and SphK2 due to its capacity to promote pancreatic survival [196]. TUDCA's activation of S1PR2-ERK1/2/AKT/SphK2/S1P is linked to chemo-drug resistance in pancreatic cells [193].…”

Section: S1p In Pancreatic Function and Cancermentioning

confidence: 99%

Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway

McGowan

Lin

Chen

2022

Cancers

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Incidence of gastrointestinal (GI) cancers is increasing, and late-stage diagnosis makes these cancers difficult to treat. Chronic and low-grade inflammation are recognized risks for most GI cancers. The GI mucosal immune system maintains healthy homeostasis and signalling molecules made from saturated fats, bioactive sphingolipids, play essential roles in healthy GI immunity. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is a key mediator in a balanced GI immune response. Disruption in the S1P pathway underlies systemic chronic metabolic inflammatory disorders, including diabetes and GI cancers, providing a strong rationale for using modulators of the S1P pathway to treat pathological inflammation. Here, we discuss the effects of bioactive sphingolipids in immune homeostasis with a focus on S1P in chronic low-grade inflammation associated with increased risk of GI carcinogenesis. Contemporary information on S1P signalling involvement in cancers of the digestive system, from top to bottom, is reviewed. Further, we discuss the use of novel S1P receptor modulators currently in clinical trials and their potential as first-line drugs in the clinic for chronic inflammatory diseases. Recently, ozanimod (ZeposiaTM) and etrasimod have been approved for clinical use to treat ulcerative colitis and eosinophilic oesophagitis, respectively, which may have longer term benefits in reducing risk of GI cancers.

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“…Till now, the synthesized TUDCA and UDCA are the only acceptable substitutes for bear bile because it has similar bioactivities as bear bile, including neuroprotective action, promoting pancreatic survival and function, and reducing gallstone formation (Lu et al 2021 ; Rosa et al 2021 ; Zangerolamo et al 2021 ). There are several methods to produce UDCA or TUDCA such as chemical synthesis, whole-cell biocatalysts, and the chemo-enzymatic method (Momose et al 1997 ; Liu et al 2013 ; Zheng et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

A green strategy to produce potential substitute resource for bear bile using engineered Saccharomyces cerevisiae

Jin

Yang

Zhao

et al. 2022

Bioresour. Bioprocess.

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Background Bear bile powder is a precious natural material characterized by high content of tauroursodeoxycholic acid (TUDCA) at a ratio of 1.00–1.50 to taurochenodeoxycholic acid (TCDCA). Results In this study, we use the crude enzymes from engineered Saccharomyces cerevisiae to directionally convert TCDCA from chicken bile powder to TUDCA at the committed ratio in vitro. This S. cerevisiae strain was modified with heterologous 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) genes. S. cerevisiae host and HSDH gene combinatorial optimization and response surface methodology was applied to get the best engineered strain and the optimal biotransformation condition, respectively, under which 10.99 ± 0.16 g/L of powder products containing 36.73 ± 6.68% of TUDCA and 28.22 ± 6.05% of TCDCA were obtained using 12.00 g/L of chicken bile powder as substrate. Conclusion This study provides a healthy and environmentally friendly way to produce potential alternative resource for bear bile powder from cheap and readily available chicken bile powder, and also gives a reference for the green manufacturing of other rare and endangered animal-derived valuable resource.

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TUDCA receptors and their role on pancreatic beta cells

Cited by 6 publications

References 52 publications

The bile acid TUDCA reduces age-related hyperinsulinemia in mice

The bile acid TUDCA reduces age-related hyperinsulinemia in mice

Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway

A green strategy to produce potential substitute resource for bear bile using engineered Saccharomyces cerevisiae

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