游离脂肪酸受体1
G蛋白偶联受体
医学
受体
2型糖尿病
葡萄糖稳态
胰岛素
肠促胰岛素
糖尿病
GPR120
药理学
2型糖尿病
生物信息学
内科学
内分泌学
胰岛素抵抗
生物
兴奋剂
作者
Julien Ghislain,Vincent Poitout
标识
DOI:10.1038/s41574-020-00459-w
摘要
Therapeutic approaches to the treatment of type 2 diabetes mellitus that are designed to increase insulin secretion either directly target β-cells or indirectly target gastrointestinal enteroendocrine cells (EECs), which release hormones that modulate insulin secretion (for example, incretins). Given that β-cells and EECs both express a large array of G protein-coupled receptors (GPCRs) that modulate insulin secretion, considerable research and development efforts have been undertaken to design therapeutic drugs targeting these GPCRs. Among them are GPCRs specific for free fatty acid ligands (lipid GPCRs), including free fatty acid receptor 1 (FFA1, otherwise known as GPR40), FFA2 (GPR43), FFA3 (GPR41) and FFA4 (GPR120), as well as the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). These lipid GPCRs have demonstrated important roles in the control of islet and gut hormone secretion. Advances in lipid GPCR pharmacology have led to the identification of a number of synthetic agonists that exert beneficial effects on glucose homeostasis in preclinical studies. Yet, translation of these promising results to the clinic has so far been disappointing. In this Review, we present the physiological roles, pharmacology and clinical studies of these lipid receptors and discuss the challenges associated with their clinical development for the treatment of type 2 diabetes mellitus.
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