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减重手术期间胰腺的非侵入性特征:循环胰腺特异性游离信使核糖核酸

Non-Invasive Characterization of the Pancreas During Bariatric Surgery Circulating Pancreatic Specific Cell-free Messenger RNA.

作者信息

Kiat Whye Kong, ShyongTai E, Shabbir Asim, Khoo Chin Meng, Koh Winston

机构信息

Molecular Engineering Lab, Institute of Molecular and Cell Biology, ASTAR, Singapore, Singapore.

Division of Endocrinology, Department of Medicine, National University Hospital, Singapore, Singapore.

出版信息

Front Genet. 2021 Oct 11;12:742496. doi: 10.3389/fgene.2021.742496. eCollection 2021.

Abstract

Bariatric surgery results in sustained weight loss and improvement in glucose homeostasis. However, the lack of accessible non-invasive tools to examine molecular alterations occurring in the pancreas limits our understanding of the causes and recovery of glucose homeostasis. Here, we describe the use of a circulating cell free mRNA (cfmRNA) based multiplex qPCR assay to selectively amplify and quantify circulating pancreatic specific transcripts levels within plasma. We applied this assay to a cohort of 58 plasma samples consisting of 10 patients that tracks multiple time points including pre and post-bariatric surgery. In our targeted multiplex screen of 14 selected pancreatic specific circulating transcripts, we identified 13 pancreatic specific transcripts that can be amplified from plasma. Furthermore, when quantifying the amplicons obtained in the short-term post-surgery (2 weeks-1 month) and long-term (3-12 months), we observed a consistent reduction of circulating GCG transcripts during short term post-surgery. Across the cohort, GCG cfmRNA levels correlated significantly with common metrics of improvement following bariatric surgery such as: haemoglobin A1c levels (R: -0.41, -value: 0.0039) and percentage of excess weight loss (R: 0.29, -value: 0.046).

摘要

减肥手术可导致体重持续减轻,并改善葡萄糖稳态。然而,缺乏可用于检测胰腺中发生的分子改变的非侵入性工具,限制了我们对葡萄糖稳态的病因及恢复情况的理解。在此,我们描述了一种基于循环游离mRNA(cfmRNA)的多重定量聚合酶链反应(qPCR)检测方法,用于选择性扩增和定量血浆中循环胰腺特异性转录本的水平。我们将该检测方法应用于一组由10名患者的58份血浆样本组成的队列中,这些样本追踪了包括减肥手术前后在内的多个时间点。在我们对14种选定的胰腺特异性循环转录本进行的靶向多重筛选中,我们鉴定出13种可从血浆中扩增的胰腺特异性转录本。此外,在对手术后短期(2周 - 1个月)和长期(3 - 12个月)获得的扩增子进行定量时,我们观察到手术后短期内循环胰高血糖素(GCG)转录本持续减少。在整个队列中,GCG cfmRNA水平与减肥手术后改善的常见指标显著相关,如:糖化血红蛋白水平(R: -0.41,P值: 0.0039)和超重减轻百分比(R:0.29,P值:0.046)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d3d/8542674/deaad5b3249a/fgene-12-742496-g001.jpg

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