scholarly journals Glucose Regulates Free Cytosolic Zn2+ Concentration, Slc39 (ZiP), and Metallothionein Gene Expression in Primary Pancreatic Islet β-Cells

2011 ◽  
Vol 286 (29) ◽  
pp. 25778-25789 ◽  
Author(s):  
Elisa A. Bellomo ◽  
Gargi Meur ◽  
Guy A. Rutter
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Β Cells ◽  
Metallothionein Gene

scholarly journals The pancreatic islet β-cell-enriched transcription factor Pdx-1 regulates Slc30a8 gene transcription through an intronic enhancer

2010 ◽  
Vol 433 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Lynley D. Pound ◽  
Yan Hang ◽  
Suparna A. Sarkar ◽  
Yingda Wang ◽  
Laurel A. Milam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Pancreatic Islet ◽  
Fusion Gene ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Β Cells ◽  
Β Cell ◽  
Specific Expression

The SLC30A8 gene encodes the zinc transporter ZnT-8, which provides zinc for insulin-hexamer formation. Genome-wide association studies have shown that a polymorphic variant in SLC30A8 is associated with altered susceptibility to Type 2 diabetes and we recently reported that glucose-stimulated insulin secretion is decreased in islets isolated from Slc30a8-knockout mice. The present study examines the molecular basis for the islet-specific expression of Slc30a8. VISTA analyses identified two conserved regions in Slc30a8 introns 2 and 3, designated enhancers A and B respectively. Transfection experiments demonstrated that enhancer B confers elevated fusion gene expression in both βTC-3 cells and αTC-6 cells. In contrast, enhancer A confers elevated fusion gene expression selectively in βTC-3 and not αTC-6 cells. These data suggest that enhancer A is an islet β-cell-specific enhancer and that the mechanisms controlling Slc30a8 expression in α- and β-cells are overlapping, but distinct. Gel retardation and ChIP (chromatin immunoprecipitation) assays revealed that the islet-enriched transcription factor Pdx-1 binds enhancer A in vitro and in situ respectively. Mutation of two Pdx-1-binding sites in enhancer A markedly reduces fusion gene expression suggesting that this factor contributes to Slc30a8 expression in β-cells, a conclusion consistent with developmental studies showing that restriction of Pdx-1 to pancreatic islet β-cells correlates with the induction of Slc30a8 gene expression and ZnT-8 protein expression in vivo.

Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells

2013 ◽  
Vol 434 (2) ◽  
pp. 370-375 ◽  
Author(s):  
Hiroko Nakabayashi ◽  
Yasuharu Ohta ◽  
Masayoshi Yamamoto ◽  
Yosuke Susuki ◽  
Akihiko Taguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Β Cells

scholarly journals Single Molecule-based FliFISH Validates Radial and Heterogeneous Gene Expression Patterns in Pancreatic Islet β Cells

Diabetes ◽  
2021 ◽  
pp. db200802
Author(s):  
Fangjia Li ◽  
Dehong Hu ◽  
Cailin Dieter ◽  
Charles Ansong ◽  
Lori Sussel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Single Molecule ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Β Cells

scholarly journals Single Molecule-based FliFISH Validates Radial and Heterogeneous Gene Expression Patterns in Pancreatic Islet β Cells

2021 ◽  
Author(s):  
Fangjia Li ◽  
Dehong Hu ◽  
Cailin Dieter ◽  
Charles Ansong ◽  
Lori Sussel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Spatial Organization ◽  
Single Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Β Cells ◽  
Β Cell ◽  
Expression Levels ◽  
Wide Range

Single cell RNA sequencing (scRNA-Seq) technologies have greatly enhanced our understanding of islet cell transcriptomes and have revealed the existence of β cell heterogeneity. However, comparison of scRNA-Seq datasets from different groups have highlighted inconsistencies in gene expression patterns, primarily due to variable detection of lower abundance transcripts. Furthermore, such analyses are unable to uncover the spatial organization of heterogeneous gene expression. Here we used fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) to quantify transcripts in single cells in mouse pancreatic islet sections. We compared the expression patterns of <i>Insulin 2</i> (<i>Ins2)</i> with <i>Mafa</i> and <i>Ucn3</i> <i>–</i> two genes expressed in β cells as they mature, as well as <i>Rgs4 – </i>a factor with variably reported expression in the islet. This approach accurately quantified transcripts across a wide range of expression levels - from single copies to over hundred copies per cell in one islet. Importantly, fliFISH allowed evaluation of transcript heterogeneity in the spatial context of an intact islet. These studies confirm the existence of a high degree of heterogeneous gene expression levels within the islet and highlight relative and radial expression patterns that likely reflect distinct β cell maturation states along the radial axis of the islet.

Meta-analysis of gene expression in human pancreatic islets after in vitro expansion

2009 ◽  
Vol 39 (1) ◽  
pp. 72-81 ◽  
Author(s):  
B. Kutlu ◽  
A. G. Kayali ◽  
S. Jung ◽  
G. Parnaud ◽  
D. Baxter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islets ◽  
Pancreatic Islet ◽  
Meta Analysis ◽  
Human Pancreas ◽  
Pancreatic Islet Transplantation ◽  
Β Cells ◽  
Human Pancreatic Islets ◽  
In Vitro Expansion

Pancreatic islet transplantation as a potential cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of β-cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional β-cells remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and for which redifferentiation was attempted. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at redifferentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increase our understanding of the active pathways in expanded and redifferentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore β-cell mass in T1D patients.

scholarly journals Single Molecule-based FliFISH Validates Radial and Heterogeneous Gene Expression Patterns in Pancreatic Islet β Cells

2021 ◽  
Author(s):  
Fangjia Li ◽  
Dehong Hu ◽  
Cailin Dieter ◽  
Charles Ansong ◽  
Lori Sussel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Spatial Organization ◽  
Single Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Β Cells ◽  
Β Cell ◽  
Expression Levels ◽  
Wide Range

Single cell RNA sequencing (scRNA-Seq) technologies have greatly enhanced our understanding of islet cell transcriptomes and have revealed the existence of β cell heterogeneity. However, comparison of scRNA-Seq datasets from different groups have highlighted inconsistencies in gene expression patterns, primarily due to variable detection of lower abundance transcripts. Furthermore, such analyses are unable to uncover the spatial organization of heterogeneous gene expression. Here we used fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) to quantify transcripts in single cells in mouse pancreatic islet sections. We compared the expression patterns of <i>Insulin 2</i> (<i>Ins2)</i> with <i>Mafa</i> and <i>Ucn3</i> <i>–</i> two genes expressed in β cells as they mature, as well as <i>Rgs4 – </i>a factor with variably reported expression in the islet. This approach accurately quantified transcripts across a wide range of expression levels - from single copies to over hundred copies per cell in one islet. Importantly, fliFISH allowed evaluation of transcript heterogeneity in the spatial context of an intact islet. These studies confirm the existence of a high degree of heterogeneous gene expression levels within the islet and highlight relative and radial expression patterns that likely reflect distinct β cell maturation states along the radial axis of the islet.

scholarly journals Pericytes contribute to the islet basement membranes to promote beta-cell gene expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lina Sakhneny ◽  
Alona Epshtein ◽  
Limor Landsman
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Basement Membranes ◽  
Cell Physiology ◽  
Β Cells ◽  
Β Cell ◽  
Cell Clustering ◽  
Β Cell Function ◽  
Cell Gene Expression ◽  
Glucose Stimulated Insulin Secretion

Abstractβ-Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate β-cells through the production of BM components. Here, we show that pericytes produce multiple components of the mouse pancreatic and islet interstitial and BM matrices. Several of the pericyte-produced ECM components were previously implicated in β-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of α2 and α4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse β-cells. Whereas α2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of β-cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion. Thus, alongside ECs, pericytes are a significant source of the islet BM, which is essential for proper β-cell function.

scholarly journals Endotoxin induction of murine metallothionein gene expression.

1990 ◽  
Vol 265 (25) ◽  
pp. 15267-15274 ◽  
Author(s):  
S.K. De ◽  
M.T. McMaster ◽  
G.K. Andrews
Keyword(s):  
Gene Expression ◽  
Metallothionein Gene

PPARγ is not required for the inhibitory actions of PGJ2 on cytokine signaling in pancreatic β-cells

2004 ◽  
Vol 286 (3) ◽  
pp. E329-E336 ◽  
Author(s):  
Sarah M. Weber ◽  
Anna L. Scarim ◽  
John A. Corbett
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Cytokine Signaling ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Inos Gene ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Inos Gene Expression

Peroxisome proliferator-activated receptor (PPAR)γ agonists, such as 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) and troglitazone, have been shown to elicit anti-inflammatory effects in pancreatic β-cells that include inhibition of cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide. In addition, these ligands impair IL-1-induced NF-κB and MAPK as well as IFN-γ-stimulated signal transducer and activator of transcription (STAT)1 activation in β-cells. The purpose of this study was to determine if PPARγ activation participates in the anti-inflammatory actions of PGJ2 in β-cells. Pretreatment of RINm5F cells for 6 h with PGJ2 results in inhibition of IL-1-stimulated IκB degradation and IFN-γ-stimulated STAT1 phosphorylation. Overexpression of a dominant-negative (dn) PPARγ mutant or treatment with the PPARγ antagonist GW-9662 does not modulate the inhibitory actions of PGJ2 on cytokine signaling in RINm5F cells. Although these agents fail to attenuate the inhibitory actions of PGJ2 on cytokine signaling, they do inhibit PGJ2-stimulated PPARγ response element reporter activity. Consistent with the inability to attenuate the inhibitory actions of PGJ2 on cytokine signaling, neither dnPPARγ nor GW-9662 prevents the inhibitory actions of PGJ2 on IL-1-stimulated iNOS gene expression or nitric oxide production by RINm5F cells. These findings support a PPARγ-independent mechanism by which PPARγ ligands impair cytokine signaling and iNOS expression by islets.

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