Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence

IF 18.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nature metabolism Pub Date : 2024-09-24 DOI:10.1038/s42255-024-01130-8
Priscila Carapeto, Kanako Iwasaki, Francesko Hela, Jiho Kahng, Ana B. Alves-Wagner, Roeland J. W. Middelbeek, Michael F. Hirshman, Guy A. Rutter, Laurie J. Goodyear, Cristina Aguayo-Mazzucato
{"title":"Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence","authors":"Priscila Carapeto, Kanako Iwasaki, Francesko Hela, Jiho Kahng, Ana B. Alves-Wagner, Roeland J. W. Middelbeek, Michael F. Hirshman, Guy A. Rutter, Laurie J. Goodyear, Cristina Aguayo-Mazzucato","doi":"10.1038/s42255-024-01130-8","DOIUrl":null,"url":null,"abstract":"Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5′-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM. Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s42255-024-01130-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5′-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM. Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
运动可激活小鼠和人类胰岛中的 AMPK,从而减少衰老
β细胞衰老是导致2型糖尿病(T2DM)的原因之一。虽然运动对 T2DM 的控制至关重要,并能显著影响细胞老化标志物,但运动对 β 细胞衰老的影响仍有待探索。在这里,我们发现在两种雌雄胰岛素抵抗小鼠模型中,短期耐力运动训练(跑步机跑步,每天 1 小时,持续 10 天)可降低β细胞衰老。体内和体外实验表明,这种效应至少部分是由训练诱导的血清胰高血糖素增加所介导的,从而激活了β细胞中的5′-AMP激活蛋白激酶(AMPK)信号。AMPK 激活导致 NRF2 核转位,衰老标记物和效应物的表达减少。值得注意的是,来自患有 T2DM 的男性和女性供体的人胰岛在接受为期 10 周的耐力运动训练后,其血清中的衰老标志物水平显著下降。这些研究结果表明,运动训练可减少胰岛的衰老,对治疗 T2DM 具有积极意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Nature metabolism
Nature metabolism ENDOCRINOLOGY & METABOLISM-
CiteScore
27.50
自引率
2.40%
发文量
170
期刊介绍: Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.
期刊最新文献
Human PERIOD3 variants lead to winter depression-like behaviours via glucocorticoid signalling AI-READI: rethinking AI data collection, preparation and sharing in diabetes research and beyond Author Correction: Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells. Diabetes, IL-10 and the brain’s microvascular crisis A pathogenic role for IL-10 signalling in capillary stalling and cognitive impairment in type 1 diabetes
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1