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首页> 外文期刊>Journal of pharmaceutical sciences. >Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders.
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Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders.

机译:游离脂肪酸受体FFAR1和GPR120作为代谢紊乱的新型治疗靶标。

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摘要

Free fatty acids (FFAs) are not only essential nutritional components, but they also act as signaling molecules in various physiological processes. Recently, a G-protein-coupled receptor deorphanizing strategy has successfully identified a family of receptors that are activated by FFAs. FFA receptors (FFARs) are proposed to play critical roles in a variety of physiological and pathophysiological processes, especially in metabolic disorders. Among the FFARs, FFAR1 (GPR40) and GPR120 are activated by medium- and long-chain FFAs. FFAR1 facilitates glucose-stimulated insulin secretion from pancreatic beta-cells, whereas GPR120 regulates the secretion of glucagon-like peptide-1 in the intestine, as well as insulin sensitivity in macrophages. Because these receptors are potential therapeutic targets for metabolic disorders such as type 2 diabetes, selective ligands have been developed. In this review, we discuss recent advances in the identification of ligands, structure activity relationships, and pharmacological characterization of FFAR1 and GPR120, and we present a summary of recent progress in understanding their physiological roles and their potential as drug targets.
机译:游离脂肪酸(FFA)不仅是必需的营养成分,而且在各种生理过程中还充当信号分子。最近,G蛋白偶联受体去孤儿策略已成功鉴定出由FFA激活的受体家族。提出FFA受体(FFAR)在多种生理和病理生理过程中,尤其是在代谢紊乱中起关键作用。在FFAR中,FFAR1(GPR40)和GPR120被中链和长链FFA激活。 FFAR1促进胰岛β细胞的葡萄糖刺激的胰岛素分泌,而GPR120调节肠中胰高血糖素样肽1的分泌以及巨噬细胞的胰岛素敏感性。由于这些受体是诸如2型糖尿病等代谢性疾病的潜在治疗靶标,因此已经开发出选择性配体。在这篇综述中,我们讨论了在FFAR1和GPR120的配体鉴定,结构活性关系和药理学表征方面的最新进展,并且我们对了解它们的生理学作用及其作为药物靶标的潜力进行了总结。

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