scholarly journals Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity

2019 ◽  
Vol 15 (7) ◽  
pp. 1472-1487 ◽  
Author(s):  
Chen Liang ◽  
Fang Hao ◽  
Xinlei Yao ◽  
Ye Qiu ◽  
Lei Liu ◽  
...  
Keyword(s):  
Erk Pathway ◽  
Β Cells ◽  
Pdx1 Expression

scholarly journals EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells

2010 ◽  
Vol 11 (1) ◽  
pp. 66 ◽  
Author(s):  
Haijuan Wang ◽  
Katarina Gambosova ◽  
Zachary A Cooper ◽  
Michael P Holloway ◽  
Andrea Kassai ◽  
...  
Keyword(s):  
Erk Pathway ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells

2021 ◽  
Author(s):  
Han Yan ◽  
Zhenzhen Chen ◽  
Haizeng Zhang ◽  
Weili Yang ◽  
Xiangyang Liu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Mitochondrial Protein ◽  
Extracellular Atp ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Intracellular Atp ◽  
Pdx1 Expression ◽  
Ca2 Channels

AbstractFAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice. In vitro, FAM3A overexpression elevated both intracellular and extracellular ATP contents and promoted PDX1 expression and insulin secretion. FAM3A-induced increase in cellular calcium (Ca2+) levels, PDX1 expression, and insulin secretion, while these were significantly repressed by inhibitors of P2 receptors or the L-type Ca2+ channels. FAM3A-induced PDX1 expression was abolished by a calmodulin inhibitor. Likewise, FAM3A-induced β-cell proliferation was also inhibited by a P2 receptor inhibitor and an L-type Ca2+ channels inhibitor. Both intracellular and extracellular ATP contributed to FAM3A-induced PDX1 expression, insulin secretion, and proliferation of pancreatic β cells.

Triiodothyronine Induces Proliferation of Pancreatic β-cells through the MAPK/ERK Pathway

2014 ◽  
Vol 122 (04) ◽  
pp. 240-245 ◽  
Author(s):  
T. Kim ◽  
J. Lee ◽  
H. Jung ◽  
T. Ha ◽  
S. Kim ◽  
...  
Keyword(s):  
Erk Pathway ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Annunziata Di Domenico ◽  
Christodoulos P. Pipinikas ◽  
Renaud S. Maire ◽  
Konstantin Bräutigam ◽  
Cedric Simillion ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Tumour Progression ◽  
Cell Of Origin ◽  
Β Cells ◽  
Mutational Spectra ◽  
Genome Wide ◽  
Pancreatic Neuroendocrine Tumours ◽  
Express Cell ◽  
Cell Type Specific ◽  
Pdx1 Expression

AbstractRecent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from α- or β-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. In the current study we examine whether tumour DNA methylation (DNAme) profiling combined with genomic data is able to identify cell of origin and to reveal pathways involved in PanNET progression. We analyse genome-wide DNAme data of 125 PanNETs and sorted α- and β-cells. To confirm cell identity, we investigate ARX and PDX1 expression. Based on epigenetic similarities, PanNETs cluster in α-like, β-like and intermediate tumours. The epigenetic similarity to α-cells progressively decreases in the intermediate tumours, which present unclear differentiation. Specific transcription factor methylation and expression vary in the respective α/β-tumour groups. Depending on DNAme similarity to α/β-cells, PanNETs have different mutational spectra, stage of the disease and prognosis, indicating potential means of PanNET progression.

Role of p38 MAPK pathway in apoptosis induction by saturated fatty acid in human pancreatic β-cells

2016 ◽  
Vol 62 (5) ◽  
pp. 13-14
Author(s):  
Jan Šrámek ◽  
Vlasta Němcová-Fürstová ◽  
Kamila Balušíková ◽  
Petr Daniel ◽  
Michael Jelínek ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Pathway ◽  
Apoptosis Induction ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Pathway Activation

Background. Pancreatic β-cells failure and apoptosis in response to chronically elevated concentrations of saturated fatty acids in blood was considered as one of the main causes of type 2 diabetes mellitus development. Although precise molecular mechanisms of this process are still unclear, there are some indications that the p38 MAPK signaling pathway could be involved.Aim, materials and methods. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in human pancreatic β-cells NES2Y. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested.Results. We have found that saturated SA at apoptosis-inducing concentration (1 mM) activated the p38 MAPK signaling pathway MKK3/6→p38 MAPK→MAPKAPK-2 and inhibited the ERK signaling pathway c-Raf→MEK1/2→ERK1/2. The inhibition of p38 MAPK expression by siRNA silencing had no significant effect on cell viability or the level of phosphorylated ERK pathway members after SA administration. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced no significant influence on cell viability or ERK pathway activation after SA exposure. The activation of p38 MAPK by the specific activator anisomycin led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members.Conclusions. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis.

scholarly journals Maturation of Adult β-Cells Revealed Using a Pdx1/Insulin Dual-Reporter Lentivirus

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1627-1635 ◽  
Author(s):  
Marta Szabat ◽  
Dan S. Luciani ◽  
James M. Piret ◽  
James D. Johnson
Keyword(s):  
Fluorescent Protein ◽  
Islet Cells ◽  
Time Lapse ◽  
Cell Phenotype ◽  
Β Cells ◽  
Β Cell ◽  
Double Positive ◽  
Min6 Cells ◽  
Dual Reporter ◽  
Pdx1 Expression

The enigmatic process of β-cell maturation has significant implications for diabetes pathogenesis, and potential diabetes therapies. This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult β-cells. Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. The majority of fluorescent cells were highly positive for both Pdx1 and insulin. Cells expressing Pdx1 but little or no insulin (Pdx1+/Inslow) comprised 15–25% of the total population. Time-lapse imaging demonstrated that Pdx1+/Inslow primary β-cells and MIN6 cells could convert to Pdx1+/Ins+ cells without cell division. Genes involved in the mature β-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1+/Ins+ cells relative to Pdx1+/Inslow cells. Conversely, genes implicated in early β-cell development (MafB, Nkx2.2) were enriched in Pdx1+/Inslow cells. Sorted Pdx1+/Inslow MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. Long-term phenotype tracking of Pdx1+/Inslow cells showed two groups, one that matured into Pdx1+/Ins+ cells and one that remained immature. These results demonstrate that adult β-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult β-cells. At a given time, a proportion of adult β-cells share similar characteristics to functionally immature embryonic β-cell progenitors. The maturation of adult β-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature β-cell genes. These results have implications for harnessing the maturation process for therapeutic purposes.

scholarly journals Pdx1 Expression in Irs2-deficient Mouse β-Cells Is Regulated in a Strain-dependent Manner

2003 ◽  
Vol 278 (44) ◽  
pp. 43691-43698 ◽  
Author(s):  
Ryo Suzuki ◽  
Kazuyuki Tobe ◽  
Yasuo Terauchi ◽  
Kajuro Komeda ◽  
Naoto Kubota ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Deficient Mouse ◽  
Β Cells ◽  
Pdx1 Expression ◽  
Strain Dependent

scholarly journals Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

2020 ◽  
Vol 295 (37) ◽  
pp. 12975-12992 ◽  
Author(s):  
Xinlei Yao ◽  
Kun Li ◽  
Chen Liang ◽  
Zilong Zhou ◽  
Jiao Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Mass ◽  
Therapeutic Use ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
And Function ◽  
Pdx1 Expression

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet β-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to β-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve β-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in β-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of β-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet β-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring β-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet β-cells both in vitro and in vivo.

scholarly journals Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression

2020 ◽  
Author(s):  
Annunziata Di Domenico ◽  
Christodoulos P. Pipinikas ◽  
Renaud Sylvain Maire ◽  
Konstantin Bräutigam ◽  
Cedric Simillion ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Tumour Progression ◽  
Cell Of Origin ◽  
Β Cells ◽  
Mutational Spectra ◽  
Genome Wide ◽  
Pancreatic Neuroendocrine Tumours ◽  
Express Cell ◽  
Cell Type Specific ◽  
Pdx1 Expression

ABSTRACTRecent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from α- or β-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. We examined whether tumour DNA methylation (DNAme) profiling combined with genomic data could identify cell of origin and reveal pathways involved in PanNET progression. We analysed genome-wide DNAme data of 125 PanNETs and sorted α- and β-cells. To confirm cell identity, we investigated ARX and PDX1 expression. Based on epigenetic similarities, PanNETs clustered in α-like, β-like and intermediate tumours. The epigenetic similarity to α-cells progressively decreased in the intermediate tumours, which presented unclear differentiation. Specific transcription factor methylation and expression varied in the respective α/β-tumour groups. Depending on DNAme similarity to α/β-cells, PanNETs have different mutational spectra, stage of the disease and prognosis, indicating potential means of PanNET progression.

Sign in / Sign up

Export Citation Format

Share Document