Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells.

Cell metabolism Pub Date : 2024-06-04 Epub Date: 2024-03-20 DOI:10.1016/j.cmet.2024.02.012
Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang
{"title":"Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells.","authors":"Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang","doi":"10.1016/j.cmet.2024.02.012","DOIUrl":null,"url":null,"abstract":"<p><p>Pancreatic β cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as β cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in β cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in β cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in β cells.</p>","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.02.012","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/20 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Pancreatic β cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as β cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in β cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in β cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in β cells.

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
细胞膜 pH 值是连接环境线索与胰岛β细胞胰岛素加工和分泌的直接纽带。
胰腺β细胞通过调节胰岛素的加工和分泌对葡萄糖波动做出积极反应。然而,这一过程是如何在多变的微环境和β细胞内在状态下进行精心调整的,以及其功能障碍是否与代谢性疾病有关,这些问题在很大程度上仍然令人难以捉摸。在这里,我们发现当葡萄糖挑战β细胞时,β细胞的细胞膜pH值(pHc)会升高,Smad5可通过其核胞质穿梭感应到这一点。如果β细胞中的Smad5发生病变,就会因胰岛素加工和分泌不足而导致高血糖和葡萄糖不耐受。Smad5 在调节胰岛素加工和分泌中的作用归因于其通过调节 V-ATP 酶活性实现颗粒酸化的非典型功能。对 Smad5 进行基因突变或给予碱性水以反映细胞膜碱化,可改善高脂饮食(HFD)处理小鼠的葡萄糖不耐受症。总之,我们的研究结果表明,pHc 是连接环境线索与 β 细胞中胰岛素加工和分泌的直接纽带。
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
自引率
0.00%
发文量
0
期刊最新文献
Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation. Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females. Serine and glycine physiology reversibly modulate retinal and peripheral nerve function. TNF compromises intestinal bile-acid tolerance dictating colitis progression and limited infliximab response. Acetate enables metabolic fitness and cognitive performance during sleep disruption.
×
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