PDF(Pubmed)
Abstract：
Incretins are gut-produced peptide-hormones that potentiate insulin secretion, especially after food intake. The concept of incretin was formed more than 100 years ago, even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes. The first incretin, glucose-dependent insulinotropic polypeptide (GIP), was identified during later 1960\'s and early 1970\'s; while the second one, known as glucagon-like peptide-1 (GLP-1), was recognized during 1980\'s. Today, GLP-1-based therapeutic agents [also known as GLP-1 receptor (GLP-1R) agonists, GLP-1RAs] are among the first line drugs for type 2 diabetes. In addition to serving as incretin, extra-pancreatic functions of GLP-1RAs have been broadly recognized, including those in the liver, despite the absence of GLP-1R in hepatic tissue. The existence of insulin-independent or gut-pancreas-liver axis-independent hepatic function of GLP-1RAs explains why those therapeutic agents are effective in subjects with insulin resistance and their profound effect on lipid homeostasis. Following a brief review on the discovery of GLP-1, we reviewed literature on the exploration of hepatic function of GLP-1 and GLP-1RAs and discussed recent studies on the role of hepatic hormone fibroblast growth factor 21 (FGF21) in mediating function of GLP-1RAs in animal models. This was followed by presenting our perspective views.
摘要：
肠促胰岛素是肠道产生的肽激素，可增强胰岛素分泌，尤其是在食物摄入后。肠促胰岛素的概念形成于100多年前，甚至在分离胰岛素并将其用于治疗1型糖尿病患者之前。第一个肠衣，葡萄糖依赖性促胰岛素多肽（GIP），在1960年代后期和1970年代早期被发现；而第二个，被称为胰高血糖素样肽-1（GLP-1），在1980年代被认可。今天,基于GLP-1的治疗剂[也称为GLP-1受体（GLP-1R）激动剂，GLP-1RAs]是2型糖尿病的一线药物之一。除了充当胰岛素外，GLP-1RAs的胰腺外功能已得到广泛认可，包括肝脏中的那些，尽管肝组织中没有GLP-1R。GLP-1RA的胰岛素非依赖性或肠-胰腺-肝轴非依赖性肝功能的存在解释了为什么这些治疗剂在具有胰岛素抗性的受试者中有效及其对脂质稳态的深远影响。在简要回顾了GLP-1的发现之后，我们回顾了有关GLP-1和GLP-1RAs的肝功能探索的文献，并讨论了肝激素成纤维细胞生长因子21（FGF21）在动物模型中介导GLP-1RAs功能的作用的最新研究。随后提出了我们的观点。
