Profiling Calcium-Dependent Gene Expression and Identifying Functional Diversity in Human Islet Cell Types

To determine whether or not any pancreatic islet cell type arises from rhombencephalic levels of neurectoderm, lengths of presumptive rhombencephalon (containing potential neural crest) of Black Australorp chick embryos at 6- to 9-somite stages were replaced isotopically and isochronically by neural tube of Japanese quail embryos. Some transplants included mesencephalic regions. In some cases various levels of the rhombencephalon were deleted and not replaced. The quail nuclear marker was detected in cranial ganglia in operated embryos sacrificed at 3¾ days of incubation and in enteric ganglia and cells accompanying some pancreatic nerves, in embryos killed at 7 days of incubation. This provided evidence of normal migration of crest cells from the grafts. Dopa was administered to the younger embryos, which were submitted to the formaldehyde-induced fluorescence procedure to demonstrate APUD (Amine Precursor Uptake and Decarboxylation) cells. No pancreatic APUD cells exhibited the quail nuclear marker. In 9- to 11-day embryos, A and B cells were identified by specific light and electron microscopic features. None showed the quail marker. The marker was also absent from those D cells seen and from cells of an as yet unidentified type, but not enough of these were found to warrant a conclusion. All islet cell types were found in embryos from which various levels of the rhombencephalon had been deleted. It is concluded that at least A and B islet cells are not derived from the rhombencephalic neurectoderm and probably not from mesencephalic levels. Their most likely origin remains the endoderm, which was the accepted source until recently

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Functional identification of islet cell types by electrophysiological fingerprinting

Journal of The Royal Society Interface ◽

10.1098/rsif.2016.0999 ◽

2017 ◽

Vol 14 (128) ◽

pp. 20160999 ◽

Cited By ~ 26

Author(s):

Linford J. B. Briant ◽

Quan Zhang ◽

Elisa Vergari ◽

Joely A. Kellard ◽

Blanca Rodriguez ◽

...

Keyword(s):

Electrical Activity ◽

Islet Cell ◽

Cell Types ◽

Cell Type ◽

Functional Identification ◽

Large Dataset ◽

Intact Mouse ◽

Whole Cell Patch Clamp ◽

Mouse Islets ◽

Islet Cell Types

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.

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The pancreatic beta cell: an intricate relation between anatomical structure, the signalling mechanism of glucose-induced insulin secretion, the low antioxidative defence, the high vulnerability and sensitivity to diabetic stress

ChemTexts ◽

10.1007/s40828-021-00140-3 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Sigurd Lenzen

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Islet Cell ◽

Pancreatic Beta Cell ◽

Cell Types ◽

Antioxidative Defence ◽

Islet Cell Types ◽

Low Expression

AbstractThe biosynthesis of insulin takes place in the insulin-producing beta cells that are organized in the form of islets of Langerhans together with a few other islet cell types in the pancreas organ. The signal for glucose-induced insulin secretion is generated in two pathways in the mitochondrial metabolism of the pancreatic beta cells. These pathways are also known as the triggering pathway and the amplifying pathway. Glucokinase, the low-affinity glucose-phosphorylating enzyme in beta cell glycolysis acts as the signal-generating enzyme in this process. ATP ultimately generated is the crucial second messenger in this process. Insulin-producing pancreatic beta cells are badly protected against oxidative stress resulting in a particular vulnerability of this islet cell type due to low expression of H2O2-inactivating enzymes in various subcellular locations, specifically in the cytosol, mitochondria, peroxisomes and endoplasmic reticulum. This is in contrast to the glucagon-producing alpha cells and other islet cell types in the islets that are well equipped with these H2O2-inactivating enzymes. On the other hand the membranes of the pancreatic beta cells are well protected against lipid peroxidation and ferroptosis through high level expression of glutathione peroxidase 4 (GPx4) and this again is at variance from the situation in the non-beta cells of the islets with a low expression level of GPx4. The weak antioxidative defence equipment of the pancreatic beta cells, in particular in states of disease, is very dangerous because the resulting particular vulnerability endangers the functionality of the beta cells, making people prone to the development of a diabetic metabolic state.

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Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide

Development ◽

10.1242/dev.118.4.1031 ◽

1993 ◽

Vol 118 (4) ◽

pp. 1031-1039 ◽

Cited By ~ 32

Author(s):

G. Teitelman ◽

S. Alpert ◽

J.M. Polak ◽

A. Martinez ◽

D. Hanahan

Keyword(s):

Neuropeptide Y ◽

Progenitor Cells ◽

Pancreatic Polypeptide ◽

Islet Cell ◽

Endocrine Pancreas ◽

Cell Types ◽

Cross Reactivity ◽

Precursor Cells ◽

Electron Microscopic ◽

Islet Cell Types

The early progenitor cells to the pancreatic islets in the mouse have been characterized so as to re-examine their possible lineage relationships to the four islet cell types found in mature islets. Insulin and glucagon were both first expressed at embryonic day 9.5, and many cells coexpressed these two markers, as shown by light and electron microscopic analysis using double-label immunohistochemistry. Incubation of embryonic pancreas with 1% glutaraldehyde, a fixative commonly used by electron microscopists, abolished this reactivity, thereby explaining reported difficulties in detecting these precursor cells. Using antisera specific for neuropeptide Y (NPY) a peptide with considerable homology to pancreatic polypeptide (PP), we show that NPY first appears with insulin and glucagon immunoreactivity at E9.5, and is co-expressed with glucagon in a majority of adult alpha cells. As we have previously reported, PP itself is first detectable immunocytochemically at postnatal day 1 with PP-specific antibodies. However, antibodies raised against bovine PP are shown by dot blotting to recognize NPY with comparable avidity, indicating that a recent report of islet progenitor cells containing PP at E9.5 (Herrera, P. L., Huarte, J., Sanvito, F., Meda, P., Orci, L. and Vassalli, J. D. (1991) Development 113, 1257–1265), actually represents cross-reactivity to NPY. The data support a model in which early precursor cells to the endocrine pancreas co-activate and co-express a set of islet cell hormone and neural genes, whose expression is both selectively increased and extinguished as development proceeds, concomitant with a restriction to the patterns of expression characteristic of mature islet cell types.

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