INS-1 832/13𝛽-Cell蛋白质组强调了脂肪酸生物合成在葡萄糖刺激胰岛素分泌中的快速调节。

IF 3.9 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Proteomics Pub Date : 2025-07-20 DOI:10.1002/pmic.70005
Nina Stremmel, Oliver Lemke, Kathrin Textoris-Taube, Daniela Ludwig, Michael Mülleder, Julia Muenzner, Markus Ralser
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引用次数: 0

摘要

胰腺细胞分泌胰岛素以应对葡萄糖水平的升高,这一过程被称为葡萄糖刺激胰岛素分泌(GSIS)。在这里,我们获得了大鼠胰腺ins - 1832 /13 β细胞的蛋白质组,这些细胞在0到20 mM的11种不同葡萄糖浓度下短期刺激,量化了3703种蛋白质的反应。蛋白质组谱的集合聚类揭示了ins - 1832 /13细胞表达的蛋白质的独特响应模式。在葡萄糖刺激下,314种蛋白质(其中包括与水疱SNARE相互作用、蛋白质输出和胰腺分泌相关的蛋白质)的丰度增加。相反,许多与代谢葡萄糖感知过程有关的蛋白质,如糖酵解、TCA循环和呼吸链,没有反应。有趣的是,我们观察到参与脂肪酸代谢的酶在完全葡萄糖饥饿释放时表现出“开启”反应,而在葡萄糖水平升高时没有进一步的变化。我们推测脂肪酸代谢活性的增加可能是GSIS的一部分,通过补充囊泡介导的胞外分泌所需的膜脂和/或通过提供电子汇来补偿葡萄糖分解代谢的增加。这些发现为β细胞功能提供了新的见解,并可能为未来糖尿病治疗中针对代谢途径的策略提供信息。摘要:我们使用高通量蛋白质组学技术捕获了INS-1 832/13 β细胞系(研究葡萄糖诱导胰岛素分泌的常用细胞模型)刺激后30分钟的全面蛋白质组变化。我们的研究结果表明,在这种细胞系中,蛋白质组的特定部分对葡萄糖暴露迅速作出反应。此外,虽然许多通常与GSIS相关的蛋白质在研究的时间框架和细胞系中丰度没有变化,但我们的研究结果将脂肪酸在胰岛素分泌的早期阶段的生物合成归因于特定的作用。通过记录INS-1 832/13 β细胞系GSIS初始阶段蛋白丰度的变化,我们的研究强调了在β细胞功能研究中取样早期时间点、良好控制的研究设计和生物重复的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An INS-1 832/13 𝛽-Cell Proteome Highlights the Rapid Regulation of Fatty Acid Biosynthesis in Glucose-Stimulated Insulin Secretion.

Pancreatic beta cells secrete insulin in response to rising glucose levels, a process known as glucose-stimulated insulin secretion (GSIS). Here, we acquire proteomes of rat pancreatic INS-1 832/13 beta cells that were short-term stimulated with 11 different glucose concentrations from 0 to 20 mM, quantifying the response of 3703 proteins. Ensemble clustering of proteome profiles revealed unique response patterns of proteins expressed by INS-1 832/13 cells. Three hundred and fourteen proteins, amongst them proteins associated with vesicular SNARE interactions, protein export, and pancreatic secretion, increased in abundance upon glucose stimulation. In contrast, many proteins implicated in metabolic glucose sensing processes such as glycolysis, the TCA cycle, and the respiratory chain, did not respond. Interestingly, we observe that enzymes participating in fatty acid metabolism showed a "switch-on" response upon release of complete glucose starvation with no further changes in abundance upon increasing glucose levels. We speculate that increased activity of fatty acid metabolic activity might either be part of GSIS by replenishing membrane lipids required for vesicle-mediated exocytosis and/or by providing an electron sink to compensate for the increase in glucose catabolism. These findings offer new insights into beta cell function and may inform future strategies for targeting metabolic pathways in diabetes treatment. SUMMARY: We used high-throughput proteomics to capture comprehensive proteome changes 30 min post stimulation in the INS-1 832/13 beta cell line, a commonly used cell model in studying glucose-induced insulin secretion. Our results show that specific parts of the proteome respond promptly upon glucose exposure in this cell line. Furthermore, while many proteins canonically associated with GSIS did not change in abundance in the time frame and cell line investigated, our results attribute a specific role to fatty acid biosynthesis in the early steps of insulin secretion. By documenting protein abundance alterations in the initial phase of GSIS in the INS-1 832/13 beta cell line, our study highlights the necessity of sampling early time points, well-controlled study design and biological replicates in the study of beta cell function.

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来源期刊
Proteomics
Proteomics 生物-生化研究方法
CiteScore
6.30
自引率
5.90%
发文量
193
审稿时长
3 months
期刊介绍: PROTEOMICS is the premier international source for information on all aspects of applications and technologies, including software, in proteomics and other "omics". The journal includes but is not limited to proteomics, genomics, transcriptomics, metabolomics and lipidomics, and systems biology approaches. Papers describing novel applications of proteomics and integration of multi-omics data and approaches are especially welcome.
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