Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications Pub Date : 2025-02-19 DOI:10.1016/j.jdiacomp.2025.108975

Qian Xu , Xuan Qiu , Hailing Di , Zhongkang Li , Zanchao Liu , Kuanzhi Liu

{"title":"Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway","authors":"Qian Xu , Xuan Qiu , Hailing Di , Zhongkang Li , Zanchao Liu , Kuanzhi Liu","doi":"10.1016/j.jdiacomp.2025.108975","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Beyond its established glucose-lowering and weight-reducing benefits, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as liraglutide may also mitigate sarcopenia. This study investigates the effects of liraglutide on diabetic sarcopenia and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A type 2 diabetic SD rat model was induced using a high-fat, high-sugar diet supplemented with a low dose of streptozotocin. Comparisons were made among control (Con), diabetic (DM), and liraglutide-treated (Li) groups for gastrocnemius muscle wet weight and length, histology (HE staining), immunofluorescence for muscle fiber typing, and Western blotting for aging-related proteins and YAP/TAZ pathway components. Concurrently, C2C12 myoblasts were differentiated into myotubes, treated with 60 mM glucose to model diabetic conditions, and assessed for morphological changes, senescence (SA-β-gal staining), and protein expression dynamics.</div></div><div><h3>Results</h3><div>Diabetic rats displayed significant reductions in muscle mass, length, and cross-sectional area, along with disorganized fiber architecture, all of which were improved by liraglutide. In vitro, C2C12 myotubes showed accelerated aging and atrophy under high-glucose conditions, which were significantly reduced by liraglutide. Analysis revealed increased expression of aging markers P53 and P21 and decreased YAP/TAZ/TEAD and Cyclin D1 levels in diabetic conditions, which were reversed following liraglutide treatment. The inhibition of YAP significantly negated the protective effects of liraglutide.</div></div><div><h3>Conclusion</h3><div>High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108975"},"PeriodicalIF":2.9000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of diabetes and its complications","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1056872725000285","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Beyond its established glucose-lowering and weight-reducing benefits, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as liraglutide may also mitigate sarcopenia. This study investigates the effects of liraglutide on diabetic sarcopenia and its underlying mechanisms.

Methods

A type 2 diabetic SD rat model was induced using a high-fat, high-sugar diet supplemented with a low dose of streptozotocin. Comparisons were made among control (Con), diabetic (DM), and liraglutide-treated (Li) groups for gastrocnemius muscle wet weight and length, histology (HE staining), immunofluorescence for muscle fiber typing, and Western blotting for aging-related proteins and YAP/TAZ pathway components. Concurrently, C2C12 myoblasts were differentiated into myotubes, treated with 60 mM glucose to model diabetic conditions, and assessed for morphological changes, senescence (SA-β-gal staining), and protein expression dynamics.

Results

Diabetic rats displayed significant reductions in muscle mass, length, and cross-sectional area, along with disorganized fiber architecture, all of which were improved by liraglutide. In vitro, C2C12 myotubes showed accelerated aging and atrophy under high-glucose conditions, which were significantly reduced by liraglutide. Analysis revealed increased expression of aging markers P53 and P21 and decreased YAP/TAZ/TEAD and Cyclin D1 levels in diabetic conditions, which were reversed following liraglutide treatment. The inhibition of YAP significantly negated the protective effects of liraglutide.

Conclusion

High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of diabetes and its complications 医学-内分泌学与代谢

CiteScore

5.90

自引率

3.30%

发文量

153

审稿时长

16 days

期刊介绍： Journal of Diabetes and Its Complications (JDC) is a journal for health care practitioners and researchers, that publishes original research about the pathogenesis, diagnosis and management of diabetes mellitus and its complications. JDC also publishes articles on physiological and molecular aspects of glucose homeostasis. The primary purpose of JDC is to act as a source of information usable by diabetes practitioners and researchers to increase their knowledge about mechanisms of diabetes and complications development, and promote better management of people with diabetes who are at risk for those complications. Manuscripts submitted to JDC can report any aspect of basic, translational or clinical research as well as epidemiology. Topics can range broadly from early prediabetes to late-stage complicated diabetes. Topics relevant to basic/translational reports include pancreatic islet dysfunction and insulin resistance, altered adipose tissue function in diabetes, altered neuronal control of glucose homeostasis and mechanisms of drug action. Topics relevant to diabetic complications include diabetic retinopathy, neuropathy and nephropathy; peripheral vascular disease and coronary heart disease; gastrointestinal disorders, renal failure and impotence; and hypertension and hyperlipidemia.