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通过电生理指纹识别胰岛细胞类型的功能鉴定

Functional identification of islet cell types by electrophysiological fingerprinting.

作者信息

Briant Linford J B, Zhang Quan, Vergari Elisa, Kellard Joely A, Rodriguez Blanca, Ashcroft Frances M, Rorsman Patrik

机构信息

Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK

Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK.

出版信息

J R Soc Interface. 2017 Mar;14(128). doi: 10.1098/rsif.2016.0999.

Abstract

The α-, β- and δ-cells of the pancreatic islet exhibit different electrophysiological features. We used a large dataset of whole-cell patch-clamp recordings from cells in intact mouse islets ( = 288 recordings) to investigate whether it is possible to reliably identify cell type (α, β or δ) based on their electrophysiological characteristics. We quantified 15 electrophysiological variables in each recorded cell. Individually, none of the variables could reliably distinguish the cell types. We therefore constructed a logistic regression model that included all quantified variables, to determine whether they could together identify cell type. The model identified cell type with 94% accuracy. This model was applied to a dataset of cells recorded from hyperglycaemic βV59M mice; it correctly identified cell type in all cells and was able to distinguish cells that co-expressed insulin and glucagon. Based on this revised functional identification, we were able to improve conductance-based models of the electrical activity in α-cells and generate a model of δ-cell electrical activity. These new models could faithfully emulate α- and δ-cell electrical activity recorded experimentally.

摘要

胰岛的α细胞、β细胞和δ细胞表现出不同的电生理特征。我们使用了来自完整小鼠胰岛细胞的全细胞膜片钳记录的大型数据集(=288次记录),以研究是否有可能根据其电生理特征可靠地识别细胞类型(α细胞、β细胞或δ细胞)。我们对每个记录的细胞中的15个电生理变量进行了量化。单独来看,没有一个变量能够可靠地区分细胞类型。因此,我们构建了一个包含所有量化变量的逻辑回归模型,以确定它们能否共同识别细胞类型。该模型识别细胞类型的准确率为94%。此模型应用于从高血糖βV59M小鼠记录的细胞数据集;它正确识别了所有细胞的类型,并且能够区分共表达胰岛素和胰高血糖素的细胞。基于这种修订后的功能识别,我们能够改进α细胞电活动的基于电导的模型,并生成δ细胞电活动的模型。这些新模型能够忠实地模拟实验记录的α细胞和δ细胞的电活动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/070c/5378133/4535a9a6d125/rsif20160999-g1.jpg

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