Ghrelin-GHSR-LEAP2 system in the pathophysiology of type 2 diabetes

作者：Yueli Pu, Jianmei Yang, Wei Li, Yi Wen, Chunmei Zheng, Yonglin Li, Lijuan Wu, Yao Ming, Chang-Ying Zhao, Chen Chen · 发表于：iScience · 年份：2025 · DOI：10.1016/j.isci.2025.113573 · 被引用次数：4 · 研究领域：Adipose Tissue and Metabolism、Pancreatic function and diabetes、Regulation of Appetite and Obesity

The Ghrelin-GHSR-LEAP2 system plays a multifaceted role in the pathophysiology of type 2 diabetes mellitus (T2DM). Ghrelin, through the activation of its receptor GHS-R1a, contributes to hyperglycemia by suppressing insulin secretion, inducing insulin resistance, and promoting hepatic glucose production. In contrast, LEAP2, an endogenous antagonist and inverse agonist of GHS-R1a, mitigates these effects by enhancing insulin secretion and improving glucose tolerance. Notably, ghrelin also demonstrates protective properties against diabetic complications through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. This duality highlights the complexity of the therapeutic targeting of the ghrelin-GHSR axis. This review provides an updated overview of the molecular mechanisms and physiological functions of the ghrelin-GHSR-LEAP2 system in T2DM and discusses the therapeutic potential and challenges of modulating this pathway.