受体
艾塞那肽
信号转导
内分泌学
内科学
肠促胰岛素
兴奋剂
利拉鲁肽
胰高血糖素样肽1受体
G蛋白偶联受体
生物
化学
2型糖尿病
细胞生物学
医学
糖尿病
作者
Ashok Mayendraraj,Mette M. Rosenkilde,Lærke S. Gasbjerg
出处
期刊:Peptides
[Elsevier]
日期:2022-05-01
卷期号:151: 170749-170749
被引量:30
标识
DOI:10.1016/j.peptides.2022.170749
摘要
Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are two class B1 G protein-coupled receptors, which are stimulated by the gastrointestinal hormones GLP-1 and GIP, respectively. In the pancreatic beta cells, activation of both receptors lead to increased cyclic adenosine monophosphate (cAMP) and glucose-dependent insulin secretion. Marketed GLP-1R agonists such as dulaglutide, liraglutide, exenatide and semaglutide constitute an expanding drug class with beneficial effects for persons suffering from type 2 diabetes and/or obesity. In recent years another drug class, the GLP-1R-GIPR co-agonists, has emerged. Especially the peptide-based, co-agonist tirzepatide is a promising candidate for a better treatment of type 2 diabetes by improving glycemic control and weight reduction. The mechanism of action for tirzepatide include biased signaling of the GLP-1R as well as potent GIPR signaling. Since the implications of co-targeting these closely related receptors concomitantly are challenging to study in vivo, the pharmacodynamic mechanisms and downstream signaling pathways of the GLP-1R-GIPR co-agonists in general, are not fully elucidated. In this review, we present the individual signaling pathways for GLP-1R and GIPR in the pancreatic beta cell with a focus on the shared signaling pathways of the two receptors and interpret the implications of GLP-1R-GIPR co-activation in the light of recent co-activating therapeutic compounds.
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