Polyclonal origin of pancreatic islets in aggregation mouse chimaeras

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1115-1121 ◽  
Author(s):  
L. Deltour ◽  
P. Leduque ◽  
A. Paldi ◽  
M.A. Ripoche ◽  
P. Dubois ◽  
...  
Keyword(s):  
Cell Division ◽  
Pancreatic Islets ◽  
Progenitor Cells ◽  
Beta Cells ◽  
Growth Pattern ◽  
Pancreatic Beta Cells ◽  
Progenitor Cell ◽  
Histological Sections ◽  
Small Clusters

In the present study, we have examined the origin and growth pattern of the beta cells in pancreatic islets, to determine whether a single progenitor cell gave rise to all the precursors of the islets, or if each of a few progenitor cells is the founder of a different islet, or if each islet is a mixture of cells originating from a pool of progenitor cells. Aggregation mouse chimaeras where the pancreatic beta cells derived from each embryo can be identified in the islets on histological sections were analyzed. In two chimaeras, all the islets contained cells from both the aggregated embryo. This clearly demonstrates that each islet resulted from several independent cells. In addition, the beta cells derived from either embryo component were in very small clusters in the islets, suggesting that in situ cell division did not account significantly for islet growth.

scholarly journals Expression of Progenitor Cell Markers During Expansion of Sorted Human Pancreatic Beta Cells

2005 ◽  
Vol 12 (2) ◽  
pp. 83-98 ◽  
Author(s):  
THOMAS BOUCKENOOGHE ◽  
BRIGITTE VANDEWALLE ◽  
ERICKA MOERMAN ◽  
PIERRE-MARIE DANZÉ ◽  
BRUNO LUKOWIAK ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Progenitor Cell ◽  
Cell Markers

Comparative toxicity of alloxan, N-alkylalloxans and ninhydrin to isolated pancreatic islets in vitro

1997 ◽  
Vol 155 (2) ◽  
pp. 283-293 ◽  
Author(s):  
A Jorns ◽  
R Munday ◽  
M Tiedge ◽  
S Lenzen
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Ultrastructural Changes ◽  
Cell Necrosis ◽  
High Concentrations ◽  
Beta Cell Necrosis

The in vitro toxicity of the diabetogenic agent alloxan as documented by the induction of beta cell necrosis was studied in isolated ob/ob mouse pancreatic islets. The effect of alloxan has been compared with that of a number of N-alkyl alloxan derivatives and with that of the structurally related compound, ninhydrin. Alloxan and its derivatives were selectively toxic to pancreatic beta cells, with other endocrine cells and exocrine parenchymal cells being well preserved, even at high concentration. In contrast, ninhydrin was selectively toxic to pancreatic beta cells only at comparatively low concentration, destroying all islet cell types at high concentrations. The ultrastructural changes induced by all the test compounds in pancreatic beta cells in vitro were very similar to those observed during the development of alloxan diabetes in vivo. The relative toxicity of the various compounds to pancreatic beta cells in vitro was not, however, related to their ability to cause diabetes in vivo. Indeed, the non-diabetogenic substances ninhydrin, N-butylalloxan and N-isobutylalloxan were very much more toxic to isolated islets than the diabetogenic compounds alloxan and N-methylalloxan. These results suggest that the differences in diabetogenicity among alloxan derivatives are not due to intrinsic differences in the susceptibility of the pancreatic beta cells to their toxicity, but may reflect differences in distribution or metabolism. High concentrations of glucose protected islets against the harmful effects of alloxan and its derivatives, but not those of ninhydrin. Low levels of glucose, and non-carbohydrate nutrients, afforded little protection, indicating that the effect of glucose is not due to the production of reducing equivalents within the cell, 3-O-Methylglucose, which protects against alloan diabetes in vivo, did not protect against alloxan toxicity in vitro. Since 3-O-methylglucose is known to prevent uptake of alloxan by pancreatic beta cells, it appears that uptake of alloxan by the cell is not a prerequisite for the induction of beta cell necrosis.

scholarly journals PCSK9 affects expression of key surface proteins in human pancreatic beta cells through intra- and extracellular regulatory circuits

2021 ◽  
Author(s):  
kevin Saitoski ◽  
Maria Ryaboshapkina ◽  
Ghaith Hamza ◽  
Andrew F Jarnuczak ◽  
claire berthault ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Cell Line ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Loss Of Function ◽  
Beta Cell Line ◽  
Gain And Loss

Aims/hypothesis: Proprotein convertase subtilisin/kexin 9 (PCSK9) is involved in the degradation of LDLR. However, PCSK9 can target other proteins in a cell-type specific manner. While PCSK9 has been detected in pancreatic islets, its expression in insulin-producing pancreatic beta cells is debated. Herein, we studied PCSK9 expression, regulation and function in the human pancreatic beta cell line EndoC-βH1. Methods: We assessed PCSK9 expression in mouse and human pancreatic islets, and in the pancreatic beta cell line EndoC-βH1. We also studied PCSK9 regulation by cholesterol, lipoproteins, Mevastatin, and by SREBPs transcription factors. To evaluate PCSK9 function in pancreatic beta cells, we performed PCSK9 gain-and loss-of-function experiments in EndoC-βH1 using siPCSK9 or recombinant PCSK9 treatments, respectively. Results: We demonstrate that PCSK9 is expressed and secreted by pancreatic beta cells. In EndoC-βH1 cells, PCSK9 expression is regulated by cholesterol and by SREBPs transcription factors. Importantly, PCSK9 knockdown results in multiple transcriptome, proteome and secretome deregulations and impaired insulin secretion. By gain- and loss-of- function experiments, we observed that PCSK9 regulates the expression levels of LDLR and VLDLR through an extracellular mechanism while CD36, PD-L1 and HLA-ABC are regulated through an intracellular mechanism. Conclusions/interpretation: Collectively, these results highlight PCSK9 as an important regulator of CD36, PD-L1 and HLA-ABC cell surface expression in pancreatic beta cells. Data availability: RNA-seq data have been deposited to GEO database with accession number GSE182016. Mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the following identifiers: PXD027921, PXD027911 and PXD027913.

scholarly journals Low-Energy Extracorporeal Shock Wave Ameliorates Streptozotocin Induced Diabetes and Promotes Pancreatic Beta Cells Regeneration in a Rat Model

2019 ◽  
Vol 20 (19) ◽  
pp. 4934 ◽  
Author(s):  
Chang-Chun Hsiao ◽  
Cheng-Chan Lin ◽  
You-Syuan Hou ◽  
Jih-Yang Ko ◽  
Ching-Jen Wang
Keyword(s):  
Pancreatic Islets ◽  
Beta Cells ◽  
Rat Model ◽  
Pancreatic Beta Cells ◽  
Urine Volume ◽  
Pancreatic Tissue ◽  
Low Energy ◽  
Insulin Production ◽  
Extracorporeal Shock Wave ◽  
Streptozotocin Induced Diabetes

Traditional therapy for diabetes mellitus has focused on supportive treatment, and is not significant in the promotion of pancreatic beta cells regeneration. We investigated the effect of low- energy extracorporeal shock wave (SW) on a streptozotocin induced diabetes (DM) rat model. Methods: The DM rats were treated with ten sessions of low-energy SW therapy (weekly for ten consecutive weeks) or left untreated. We assessed blood glucose, hemoglobin A1c (HbA1c), urine volume, pancreatic islets area, c-peptide, glucagon-like peptide 1 (GLP-1) and insulin production, beta cells number, pancreatic tissue inflammation, oxidative stress, apoptosis, angiogenesis, and stromal cell derived factor 1 (SDF-1) ten weeks after the completion of treatment. Results: The ten- week low-energy SW therapy regimen significantly reduced blood glucose, HbA1c, and urine volume as well as significantly enhancing pancreatic islets area, c-peptide, GLP-1, and insulin production in the rat model of DM. Moreover, low-energy SW therapy increased the beta cells number in DM rats. This was likely primarily attributed to the fact that low-energy SW therapy reduced pancreatic tissue inflammation, apoptosis, and oxidative stress as well as increasing angiogenesis, cell proliferation, and tissue repair potency. Conclusions: Low-energy SW therapy preserved pancreatic islets function in streptozotocin-induced DM. Low-energy SW therapy may serve as a novel noninvasive and effective treatment of DM.

scholarly journals Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations

2009 ◽  
Vol 297 (1) ◽  
pp. G197-G206 ◽  
Author(s):  
Lisa Mee ◽  
Svetlana M. Nabokina ◽  
V. Thillai Sekar ◽  
Veedamali S. Subramanian ◽  
Kathrin Maedler ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Endocrine Pancreas ◽  
Normal Function ◽  
Confocal Imaging ◽  
Mrna Levels ◽  
Uptake Mechanism ◽  
Human Pancreatic Islets ◽  
Primary Mouse

Thiamin is essential for the normal function of the endocrine pancreas, but very little is known about uptake mechanism(s) and regulation by beta cells. We addressed these issues using mouse-derived pancreatic beta-TC-6 cells, and freshly isolated primary mouse and human pancreatic islets. Results showed that thiamin uptake by beta-TC-6 cells involves a pH (but not Na+)-dependent carrier-mediated process that is saturable at both the nanomolar (apparent Km = 37.17 ± 9.9 nM) and micromolar (apparent Km = 3.26 ± 0.86 μM) ranges, cis-inhibited by thiamin structural analogs, and trans-stimulated by unlabeled thiamin. Involvement of carrier-mediated process was also confirmed in primary mouse and human pancreatic islets. Both THTR-1 and THTR-2 were found to be expressed in these mouse and human pancreatic preparations. Maintaining beta-TC-6 cells in the presence of a high level of thiamin led to a significant ( P < 0.01) decrease in thiamin uptake, which was associated with a significant downregulation in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels and a decrease in transcriptional (promoter) activity. Modulators of intracellular Ca2+/calmodulin- and protein-tyrosine kinase-mediated pathways also altered thiamin uptake. Finally, confocal imaging of live beta-TC-6 cells showed that clinical mutants of THTR-1 have mixed expression phenotypes and all led to impairment in thiamin uptake. These studies demonstrate for the first time that thiamin uptake by the endocrine pancreas is carrier mediated and is adaptively regulated by the prevailing vitamin level via transcriptional mechanisms. Furthermore, clinical mutants of THTR-1 impair thiamin uptake via different mechanisms.

scholarly journals MicroRNAs Regulate the Wnt/Ca2+ Signaling Pathway to Promote the Secretion of Insulin in Pancreatic Nestin-Positive Progenitor Cells

2014 ◽  
Author(s):  
Chunyu Bai ◽  
Xiangchen Li ◽  
Yuhua Gao ◽  
Taofeng Lu ◽  
Kunfu Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Progenitor Cells ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Target Genes ◽  
Cell Function ◽  
Expression Profiles ◽  
Control Cell ◽  
Small Noncoding Rnas ◽  
And Function

MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3?-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.

Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 999-1008 ◽  
Author(s):  
S. Temple ◽  
A.A. Davis
Keyword(s):  
Cell Division ◽  
Progenitor Cells ◽  
Associated Factors ◽  
Progenitor Cell ◽  
Ventricular Zone ◽  
Single Cells ◽  
Cell Phenotype ◽  
Cortical Progenitor

Ventricular zone cells in the developing CNS undergo extensive cell division in vivo and under certain conditions in vitro. The culture conditions that promote cell division have been studied to determine the role that contact with cell membrane associated factors play in the proliferation of these cells. Progenitor cells have been taken from the ventricular zone of developing rat cerebral cortex and placed into microwells. Small clusters of these cells can generate large numbers of neurons and non-neuronal progeny. In contrast, single progenitor cells largely cease division, approximately 90% acquiring neuron-like characteristics by 1 day in vitro. DiI-labeled, single cells from embryonic day 14 cortex plated onto clusters of unmarked progenitor cells have a significantly higher probability (approximately 3-fold) of maintaining a progenitor cell phenotype than if plated onto the plastic substratum around 100 microns away from the clusters. Contact with purified astrocytes also promotes the progenitor cell phenotype, whereas contact with meningeal fibroblasts or balb3T3 cells promotes their differentiation. Membrane homogenates from cortical astrocytes stimulate significantly more incorporation of BrdU by E14 cortical progenitor cells than membrane homogenates from meningeal fibroblasts. These data indicate that the proliferation of rat cortical progenitor cells can be maintained by cell-type specific, membrane-associated factors.

In situ characterization of nonmitochondrial Ca2+ stores in individual pancreatic beta-cells

Diabetes ◽  
1998 ◽  
Vol 47 (8) ◽  
pp. 1224-1230 ◽  
Author(s):  
A. Tengholm ◽  
C. Hagman ◽  
E. Gylfe ◽  
B. Hellman
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
In Situ Characterization

scholarly journals Immunocytochemical localization of alpha-protein kinase C in rat pancreatic beta-cells during glucose-induced insulin secretion.

1992 ◽  
Vol 119 (2) ◽  
pp. 313-324 ◽  
Author(s):  
S Ganesan ◽  
R Calle ◽  
K Zawalich ◽  
K Greenawalt ◽  
W Zawalich ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Periphery ◽  
Rat Pancreatic Islets ◽  
Kinase C ◽  
Isolated Rat

To investigate the role of protein kinase C (PKC) in the regulation of insulin secretion, we visualized changes in the intracellular localization of alpha-PKC in fixed beta-cells from both isolated rat pancreatic islets and the pancreas of awake unstressed rats during glucose-induced insulin secretion. Isolated, perifused rat islets were fixed in 4% paraformaldehyde, detergent permeabilized, and labeled with a mAb specific for alpha-PKC. The labeling was visualized by confocal immunofluorescent microscopy. In isolated rat pancreatic islets perifused with 2.75 mM glucose, alpha-PKC immunostaining was primarily cytoplasmic in distribution throughout the beta-cells. In islets stimulated with 20 mM glucose, there was a significant redistribution of alpha-PKC to the cell periphery. This glucose-induced redistribution was abolished when either mannoheptulose, an inhibitor of glucose metabolism, or nitrendipine, an inhibitor of calcium influx, were added to the perifusate. We also examined changes in the intracellular distribution of alpha-PKC in the beta-cells of awake, unstressed rats that were given an intravenous infusion of glucose. Immunocytochemical analysis of pancreatic sections from these rats demonstrated a glucose-induced translocation of alpha-PKC to the cell periphery of the beta-cells. These results demonstrate that the metabolism of glucose can induce the redistribution of alpha-PKC to the cell periphery of beta-cells, both in isolated islets and in the intact animal, and suggest that alpha-PKC plays a role in mediating glucose-induced insulin secretion.

scholarly journals Quick-freeze fixation and freeze-drying of isolated rat pancreatic islets: application to the ultrastructural localization of inorganic phosphate in the pancreatic beta cell.

1981 ◽  
Vol 29 (2) ◽  
pp. 321-325 ◽  
Author(s):  
R W Dudek ◽  
A F Boyne ◽  
N Freinkel
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Inorganic Phosphate ◽  
Freeze Drying ◽  
Secretory Granules ◽  
Pancreatic Beta Cell ◽  
Ultrastructural Localization ◽  
Freeze Fixation

A bounce-free mechanical quick-freeze assembly and a Coulter-Terracio freeze-dry apparatus were successfully coupled to obtain high quality ultrastructural preservation of pancreatic beta cells in a simple and dependable manner. Except for obvious shrinkage spaces, morphological relationships at the tissue, cellular, and subcellular levels were all intact. Beta cell secretory granules demonstrated a dense core surrounded by an electron lucent halo as typically described in specimens after aqueous fixation. Cell membranes and intracellular membranes demonstrated a trilaminar appearance. Golgi apparatus were well preserved. Two clearly defined populations of mitochondria were found. One group of very dark mitochondria had extremely dense matrices in which cristae were barely visible. A second group of mitochondria had light matrices with prominent cristae. The combined quick-freeze fixation and freeze-drying was applied to reevaluate the ultrastructural localization of inorganic phosphate that had been precipitated with lead in the beta cells of pancreatic islets. Accumulation of inorganic phosphate adjacent to the plasma membrane and over the nucleolus of the beta cell in nonstimulated islets was documented with better detail than heretofore possible.

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