scholarly journals The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress

2021 ◽  
Author(s):  
Mireille M.J.P.E. Sthijns ◽  
Timo Rademakers ◽  
Jolien Oosterveer ◽  
Thomas Geuens ◽  
Clemens A. van Blitterswijk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Islet Cell ◽  
Monolayer Culture ◽  
Three Dimensional ◽  
Cell Types ◽  
Pancreatic Islets Of Langerhans ◽  
Endogenous Antioxidant ◽  
Islet Cell Types ◽  
Insight Into

AbstractThe pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.

scholarly journals 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 ◽  
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.

scholarly journals Protein-Mediated Interactions of Pancreatic Islet Cells

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-22 ◽  
Author(s):  
Paolo Meda
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Islet Cell ◽  
Islet Cells ◽  
Cell Communication ◽  
Cell Types ◽  
Integral Membrane Protein ◽  
Normal Function ◽  
Cell Functions ◽  
Islet Cell Types

The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions. Among these, several mechanisms depend on different families of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin, and claudins) and paracrine communications (pannexins) between beta cells, and between these cells and the other islet cell types. Also, other proteins (integrins) provide communication of the different islet cell types with the materials that form the islet basal laminae and extracellular matrix. Here, we review what is known about these proteins and their signaling in pancreaticβ-cells, with particular emphasis on the signaling provided by Cx36, given that this is the integral membrane protein involved in cell-to-cell communication, which has so far been mostly investigated for effects on beta cell functions.

scholarly journals Three-dimensional testicular organoids as novel in vitro models of testicular biology and toxicology

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Sadman Sakib ◽  
Anna Voigt ◽  
Taylor Goldsmith ◽  
Ina Dobrinski
Keyword(s):  
Reproductive Biology ◽  
Monolayer Culture ◽  
Three Dimensional ◽  
Cell Types ◽  
In Vitro Models ◽  
Toxicity Screening ◽  
Current State ◽  
Potential Applications ◽  
Multiple Cell

Abstract Organoids are three dimensional structures consisting of multiple cell types that recapitulate the cellular architecture and functionality of native organs. Over the last decade, the advent of organoid research has opened up many avenues for basic and translational studies. Following suit of other disciplines, research groups working in the field of male reproductive biology have started establishing and characterizing testicular organoids. The three-dimensional architectural and functional similarities of organoids to their tissue of origin facilitate study of complex cell interactions, tissue development and establishment of representative, scalable models for drug and toxicity screening. In this review, we discuss the current state of testicular organoid research, their advantages over conventional monolayer culture and their potential applications in the field of reproductive biology and toxicology.

Simultaneous Assessment of Prohormone Transport and Processing in Four Separate Islet Cell Types

Pancreas ◽  
1988 ◽  
Vol 3 (6) ◽  
pp. 700-713 ◽  
Author(s):  
Bryan D. Noe ◽  
Mylene Amherdt ◽  
Alain Perrelet ◽  
Lelio Orci
Keyword(s):  
Islet Cell ◽  
Cell Types ◽  
Islet Cell Types ◽  
Simultaneous Assessment

scholarly journals GeneSpeed Beta Cell: An Online Genomics Data Repository and Analysis Resource Tailored for the Islet Cell Biologist

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Nayeem Quayum ◽  
Alecksandr Kutchma ◽  
Suparna A. Sarkar ◽  
Kirstine Juhl ◽  
Gerard Gradwohl ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Biology ◽  
Islet Cell ◽  
Gene Array ◽  
Protein Domain ◽  
Data Repository ◽  
Separate Component ◽  
Type Data ◽  
Design And Methods ◽  
Insight Into

Objective. We here describe the development of a freely available online database resource, GeneSpeed Beta Cell, which has been created for the pancreatic islet and pancreatic developmental biology investigator community.Research Design and Methods. We have developed GeneSpeed Beta Cell as a separate component of the GeneSpeed database, providing a genomics-type data repository of pancreas and islet-relevant datasets interlinked with the domain-oriented GeneSpeed database.Results. GeneSpeed Beta Cell allows the query of multiple published and unpublished select genomics datasets in a simultaneous fashion (multiexperiment viewing) and is capable of defining intersection results from precomputed analysis of such datasets (multidimensional querying). Combined with the protein-domain categorization/assembly toolbox provided by the GeneSpeed database, the user is able to define spatial expression constraints of select gene lists in a relatively rigid fashion within the pancreatic expression space. We provide several demonstration case studies of relevance to islet cell biology and development of the pancreas that provide novel insight into islet biology.Conclusions. The combination of an exhaustive domain-based compilation of the transcriptome with gene array data of interest to the islet biologist affords novel methods for multidimensional querying between individual datasets in a rapid fashion, presently not available elsewhere.

scholarly journals Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

2006 ◽  
Vol 80 (11) ◽  
pp. 5637-5643 ◽  
Author(s):  
Toru Kanno ◽  
Kisoon Kim ◽  
Ken Kono ◽  
Kristen M. Drescher ◽  
Nora M. Chapman ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Cultures ◽  
Virulent Strain ◽  
Nod Mice ◽  
Cell Types ◽  
Rapid Onset ◽  
Infectious Dose ◽  
Group B ◽  
Islet Cell Types

ABSTRACT Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5′-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.

An experimental investigation into the possible origin of pancreatic islet cells from rhombencephalic neurectoderm

Development ◽  
1979 ◽  
Vol 52 (1) ◽  
pp. 23-38
Author(s):  
Ann Andrew ◽  
Beverley Kramer
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Islet Cells ◽  
Cell Types ◽  
Nuclear Marker ◽  
Electron Microscopic ◽  
Pancreatic Islet Cell ◽  
Enteric Ganglia ◽  
Microscopic Features ◽  
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

scholarly journals Functional identification of islet cell types by electrophysiological fingerprinting

2017 ◽  
Vol 14 (128) ◽  
pp. 20160999 ◽  
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.

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

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1031-1039 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document