Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities

胆汁酸与2型糖尿病:在葡萄糖稳态中的作用及治疗契机

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Abstract

BACKGROUND: Type 2 diabetes mellitus (T2DM), characterized by impaired glucose homeostasis, represents a significant threat to public health. Bile acids (BAs), as key metabolic regulators, play an essential role in glucose metabolism. Recent advances in high-resolution metabolomics have revealed that various BA species are closely linked to T2DM pathogenesis and play a critical role in maintaining glucose homeostasis. Understanding the underlying mechanisms by which BAs modulate glucose metabolism provides valuable insights for the prevention and treatment of T2DM. METHODS/RESULTS: This review describes the roles of diverse BA species in regulating glucose metabolism and comprehensively summarizes the relationship of unconjugated and conjugated BAs with T2DM in population studies. Furthermore, we discuss BA-targeted therapeutic approaches for T2DM, highlighting the urgent need for developing tissue-restricted modulators of BA receptors and advancing the clinical translation of novel beneficial BAs. CONCLUSION: Deeply understanding the role of BAs played in the pathogenesis and progression of T2DM will facilitate the development of potential therapeutic agents.

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