| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 8. |
- Briant, L., et al.
(författare)
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Glucagon secretion from pancreatic alpha-cells
- 2016
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:2, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes involves a menage a trois of impaired glucose regulation of pancreatic hormone release: in addition to impaired glucose-induced insulin secretion, the release of the hyperglycaemic hormone glucagon becomes dysregulated; these last-mentioned defects exacerbate the metabolic consequences of hypoinsulinaemia and are compounded further by hypersecretion of somatostatin (which inhibits both insulin and glucagon secretion). Glucagon secretion has been proposed to be regulated by either intrinsic or paracrine mechanisms, but their relative significance and the conditions under which they operate are debated. Importantly, the paracrine and intrinsic modes of regulation are not mutually exclusive; they could operate in parallel to control glucagon secretion. Here we have applied mathematical modelling of alpha-cell electrical activity as a novel means of dissecting the processes that underlie metabolic regulation of glucagon secretion. Our analyses indicate that basal hypersecretion of somatostatin and/or increased activity of somatostatin receptors may explain the loss of adequate counter regulation under hypoglycaemic conditions, as well as the physiologically inappropriate stimulation of glucagon secretion during hyperglycaemia seen in diabetic patients. We therefore advocate studying the interaction of the paracrine and intrinsic mechanisms; unifying these processes may give a more complete picture of the regulation of glucagon secretion from alpha-cells than studying the individual parts.
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| 9. |
- Briant, L. J. B., et al.
(författare)
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Functional identification of islet cell types by electrophysiological fingerprinting
- 2017
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 14:128
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Tidskriftsartikel (refereegranskat)abstract
- The alpha-, beta- and delta-cells of the pancreatic islet exhibit different electrophysiological features. We used a large dataset of whole- cell patch- clamp recordings from cells in intactmouse islets (N = 288 recordings) to investigatewhether it is possible to reliably identify cell type (alpha,beta or gamma) 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 regressionmodel that included all quantified variables, to determine whether they could together identify cell type. The model identified cell typewith 94% accuracy. Thismodelwas applied to a dataset of cells recorded from hyperglycaemic bV59M 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 alpha-cells and generate a model of gamma-cell electrical activity. These new models could faithfully emulate alpha- and gamma-cell electrical activity recorded experimentally.
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| 10. |
- Hamilton, Alexander, et al.
(författare)
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Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells
- 2019
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Ingår i: Jove-Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :153
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islet hormones regulate blood glucose homeostasis. Changes in blood glucose induce oscillations of cytosolic calcium in pancreatic islet cells that trigger secretion of three main hormones: insulin (from beta-cells), glucagon (alpha-cells) and somatostatin (delta-cells). beta-Cells, which make up the majority of islet cells and are electrically coupled to each other, respond to the glucose stimulus as one single entity. The excitability of the minor subpopulations, alpha-cells and delta-cells (making up around 20% (30%) and 4% (10%) of the total rodent(1) (human(2)) islet cell numbers, respectively) is less predictable and is therefore of special interest. Calcium sensors are delivered into the peripheral layer of cells within the isolated islet. The islet or a group of islets is then immobilized and imaged using a fluorescence microscope. The choice of the imaging mode is between higher throughput (wide-field) and better spatial resolution (confocal). Conventionally, laser scanning confocal microscopy is used for imaging tissue, as it provides the best separation of the signal between the neighboring cells. A wide-field system can be utilized too, if the contaminating signal from the dominating population of beta-cells is minimized. Once calcium dynamics in response to specific stimuli have been recorded, data are expressed in numerical form as fluorescence intensity vs. time, normalized to the initial fluorescence and baseline-corrected, to remove the effects linked to bleaching of the fluorophore. Changes in the spike frequency or partial area under the curve (pAUC) are computed vs. time, to quantify the observed effects. pAUC is more sensitive and quite robust whereas spiking frequency provides more information on the mechanism of calcium increase. Minor cell subpopulations can be identified using functional responses to marker compounds, such as adrenaline and ghrelin, that induce changes in cytosolic calcium in a specific populations of islet cells.
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