Effects of tauroursodeoxycholic acid on glucose homeostasis: Potential binding of this bile acid with the insulin receptor

Silva, Joel A. da; Figueiredo, Letícia S.; Chaves, Janaína O.; Oliveira, Kênia M.; Carneiro, Everardo M.; Abreu, Paula Alvarez; Ribeiro, Rosane Aparecida

doi:10.1016/j.lfs.2021.120020

Cited by 16 publications

(7 citation statements)

References 44 publications

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“…TGR5, and nuclear receptors e.g. FXR, both of which regulate metabolisms of glucose and lipids and control bile acid transportation and turnover [ 26 , 27 ]. In addition, TUDCA reduces cell mortality by reducing oxidative stress independent of ER stress [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Zhang

Yang²,

Liu³

et al. 2022

Redox Biology

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Section: Discussionmentioning

confidence: 99%

Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Zhang

Yang²,

Liu³

et al. 2022

Redox Biology

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“…In agreement, by modulating ER stress, administration of TUDCA in obese and type 2 diabetic mice normalized glycemia, restored insulin sensitivity in liver, muscle and adipose tissues, as well as reduced fatty liver disease ( 92 ). Of note, TUDCA may act as an insulin receptor (IR) agonist, which, in addition, can contribute to its beneficial effects on insulin sensitivity ( 93 ).…”

Section: Actions Of Tudca In Adipositymentioning

confidence: 99%

Insights by which TUDCA is a potential therapy against adiposity

et al. 2023

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Adipose tissue is an organ with metabolic and endocrine activity. White, brown and ectopic adipose tissues have different structure, location, and function. Adipose tissue regulates energy homeostasis, providing energy in nutrient-deficient conditions and storing it in high-supply conditions. To attend to the high demand for energy storage during obesity, the adipose tissue undergoes morphological, functional and molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a molecular hallmark of metabolic disorders. In this sense, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), a bile acid conjugated to taurine with chemical chaperone activity, has emerged as a therapeutic strategy to minimize adipose tissue dysfunction and metabolic alterations associated with obesity. In this review, we highlight the effects of TUDCA and receptors TGR5 and FXR on adipose tissue in the setting of obesity. TUDCA has been demonstrated to limit metabolic disturbs associated to obesity by inhibiting ER stress, inflammation, and apoptosis in adipocytes. The beneficial effect of TUDCA on perivascular adipose tissue (PVAT) function and adiponectin release may be related to cardiovascular protection in obesity, although more studies are needed to clarify the mechanisms. Therefore, TUDCA has emerged as a potential therapeutic strategy for obesity and comorbidities.

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“…We have summarized the hypoglycemic mechanisms and glucose outcomes of bile acid-related drugs, as shown in Table 1. In these studies, BAs (CDCA [42,43], TUDCA [31,44,45], HCA [46], GUDCA [47]), FXR inhibitors (HS218 [48], Gly-MCA [49,50]), FXR agonists (Fexaramine [51,52], GW4064 [53,54]), FXR/TGR5 agonists (INT-767 [55]), TGR5 agonists (INT-777 [52], RO5527239 [52]), and clinical drugs (Colesevelam [56], Metformin [37,57,58], Acarbose [41], Obeticholic acid (OCA) [59][60][61]) all demonstrated hypoglycemic effects by activating different mechanisms. However, one study found that blood glucose increased in mice treated with GW4064 [62].…”

Section: Bile Acids and Diabetes Drugs (Metformin And Acarbose)mentioning

confidence: 99%

“…Currently, the research is primarily focused on changes in bile acid composition and the effects of the bile acid signaling pathways on blood glucose. The pathways involved include the BA-FXR-SHP pathway [48,51,53], BA-FXR-FGFR15/19 pathway [77,85,86], BA-TGR5-GLP-1 pathway [7,87,88] and BA-TGR5-cAMP pathway [43,44,52]. Through these various pathways, the ultimate outcome is a modification in bile acid composition, a reductionin in the ratio of 12 α-hydroxylated BAs to non-12 α-hydroxylated BAs, an improvement in insulin resistance, and a decrease in liver gluconeogenesis and insulin sensitivity in adipose tissue.…”

Section: Hypoglycemic Mechanism Of Bile Acidmentioning

confidence: 99%

Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus

Hou,

Zhai,

Wang

et al. 2023

Diabetol Metab Syndr

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Bile acids, which are steroid molecules originating from cholesterol and synthesized in the liver, play a pivotal role in regulating glucose metabolism and maintaining energy balance. Upon release into the intestine alongside bile, they activate various nuclear and membrane receptors, influencing crucial processes. These bile acids have emerged as significant contributors to managing type 2 diabetes mellitus, a complex clinical syndrome primarily driven by insulin resistance. Bile acids substantially lower blood glucose levels through multiple pathways: BA-FXR-SHP, BA-FXR-FGFR15/19, BA-TGR5-GLP-1, and BA-TGR5-cAMP. They also impact blood glucose regulation by influencing intestinal flora, endoplasmic reticulum stress, and bitter taste receptors. Collectively, these regulatory mechanisms enhance insulin sensitivity, stimulate insulin secretion, and boost energy expenditure. This review aims to comprehensively explore the interplay between bile acid metabolism and T2DM, focusing on primary regulatory pathways. By examining the latest advancements in our understanding of these interactions, we aim to illuminate potential therapeutic strategies and identify areas for future research. Additionally, this review critically assesses current research limitations to contribute to the effective management of T2DM.

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Effects of tauroursodeoxycholic acid on glucose homeostasis: Potential binding of this bile acid with the insulin receptor

Cited by 16 publications

References 44 publications

Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice

Insights by which TUDCA is a potential therapy against adiposity

Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus

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