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

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-15 DOI:10.1016/j.isci.2025.113573

Yueli Pu , Jianmei Yang , Wei Li , Yi Wen , Chunmei Zheng , Yonglin Li , Lijuan Wu , Yao Ming , Changying Zhao , Chen Chen

引用次数: 0

Abstract

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.

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Ghrelin-GHSR-LEAP2系统在2型糖尿病病理生理中的作用

Ghrelin-GHSR-LEAP2系统在2型糖尿病（T2DM）的病理生理中起着多方面的作用。Ghrelin通过激活其受体GHS-R1a，抑制胰岛素分泌，诱导胰岛素抵抗，促进肝脏葡萄糖生成，从而导致高血糖。相比之下，GHS-R1a的内源性拮抗剂和逆激动剂LEAP2通过增强胰岛素分泌和改善葡萄糖耐量来减轻这些影响。值得注意的是，胃饥饿素还通过抗炎、抗氧化和抗凋亡机制显示出对糖尿病并发症的保护作用。这种双重性突出了ghrelin-GHSR轴治疗靶向的复杂性。本文综述了ghrelin-GHSR-LEAP2系统在T2DM中的分子机制和生理功能，并讨论了调节该通路的治疗潜力和挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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