多肽 N-乙酰半乳糖氨酰基转移酶 14 是胰腺 β 细胞功能和生长的新型介质

IF 3.8 3区 医学 Q2 CELL BIOLOGY
Tingting Shu , Yan Zhang , Tong Sun , Yunxia Zhu
{"title":"多肽 N-乙酰半乳糖氨酰基转移酶 14 是胰腺 β 细胞功能和生长的新型介质","authors":"Tingting Shu ,&nbsp;Yan Zhang ,&nbsp;Tong Sun ,&nbsp;Yunxia Zhu","doi":"10.1016/j.mce.2024.112269","DOIUrl":null,"url":null,"abstract":"<div><p>Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of <em>Ganlt14</em> was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that <em>Galnt14</em> was mainly expressed in β cells of mouse islets. <em>Galnt14</em> knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth\",\"authors\":\"Tingting Shu ,&nbsp;Yan Zhang ,&nbsp;Tong Sun ,&nbsp;Yunxia Zhu\",\"doi\":\"10.1016/j.mce.2024.112269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of <em>Ganlt14</em> was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that <em>Galnt14</em> was mainly expressed in β cells of mouse islets. <em>Galnt14</em> knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.</p></div>\",\"PeriodicalId\":18707,\"journal\":{\"name\":\"Molecular and Cellular Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-05-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0303720724001254\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0303720724001254","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

多肽 N-乙酰半乳糖氨酰转移酶 14(GALNT14)在癌症进展和化疗反应中发挥着重要作用。在这里,我们发现 GALNT14 在胰腺 β 细胞中高表达,并调控 β 细胞的功能和生长。我们发现,在三种啮齿类 2 型糖尿病模型的原代胰岛中,Ganlt14 的表达水平明显下降。单细胞测序确定了Galnt14主要在小鼠胰岛β细胞中表达。利用CRISPR/Cas9技术构建的Galnt14基因敲除(G14KO)INS-1细胞系生长正常,但形状变钝,基础胰岛素分泌增加。蛋白质组学和糖蛋白组学联合研究表明,G14KO 改变了细胞间的连接、交流和粘附。胰岛素受体(IR)和 IGF1-1R 被间接证实为 GALNT14 的底物,有助于降低 IGF1 诱导的 p-AKT 水平和 G14KO 细胞的细胞生长。总之,这项研究发现,GALNT14是调节β细胞生物学的新型调节因子,为β细胞O-糖基化与糖尿病的发生提供了一个缺失的环节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth

Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth

Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that Galnt14 was mainly expressed in β cells of mouse islets. Galnt14 knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信