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 (N = 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.
Highlights
The pancreatic islet is composed of three main cell types: a, b- and d-cells [1,2]
Cell capacitance (Ccell) in b-cells (5.8 + 0.3 pF, N 1⁄4 56) was significantly larger than that seen in a-cells (4.2 + 0.1 pF, N 1⁄4 141; p, 0.001) and d-cells (4.3 + 0.1 pF, N 1⁄4 91; p, 0.001; figure 1a). a-Cells and d-cells did not differ in their cell size ( p 1⁄4 0.556)
By constructing a multinomial logistic regression model, that multiple electrophysiological variables can be used to predict islet cell type with 94% accuracy
Summary
All three cell types are electrically excitable and use electrical signals to regulate hormone release [3,4,5]. These hormones—glucagon, insulin and somatostatin, respectively—all have a role in normalizing plasma glucose [6,7,8]. In type 2 diabetes mellitus (T2DM), both glucagon and insulin secretion are impaired [9,10]. This impairment has been linked to changes in the electrical properties of a- and b-cells [11,12,13,14]. Determining the mechanisms by which islet cells couple electrical activity to hormone secretion is fundamental for understanding normal glucose homeostasis and the pathophysiology of T2DM
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