2123-P: Peroxiredoxin6 Is a Novel Promoter of Pancreatic Beta-Cell Survival

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2123-P
Author(s):  
FRANCESCA PACIFICI ◽  
DAVID DELLA-MORTE ◽  
BARBARA CAPUANI ◽  
DONATELLA PASTORE ◽  
ROBERTO ARRIGA ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell

W46 ROLE OF LIPOPROTEINS IN PANCREATIC BETA-CELL SURVIVAL, PROLIFERATION AND FUNCTION

2010 ◽  
Vol 11 (2) ◽  
pp. 10
Author(s):  
R.A. Sibler ◽  
S. Rütti ◽  
J.A. Ehses ◽  
R. Prazak ◽  
D.T. Meier ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
And Function

scholarly journals Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines

2021 ◽  
Author(s):  
Paola Benaglio ◽  
Han Zhu ◽  
Mei-Lin Okino ◽  
Jian Yan ◽  
Ruth Elgamal ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Survival ◽  
Beta Cells ◽  
High Throughput ◽  
Proinflammatory Cytokines ◽  
Pancreatic Beta Cell ◽  
Regulatory Elements ◽  
A Genome

Beta cells intrinsically contribute to the pathogenesis of type 1 diabetes (T1D), but the genes and molecular processes that mediate beta cell survival in T1D remain largely unknown. We combined high throughput functional genomics and human genetics to identify T1D risk loci regulating genes affecting beta cell survival in response to the proinflammatory cytokines IL-1b, IFNg, and TNFa. We mapped 38,931 cytokine-responsive candidate cis-regulatory elements (cCREs) active in beta cells using ATAC-seq and single nuclear ATAC-seq (snATAC-seq), and linked cytokine-responsive beta cell cCREs to putative target genes using single cell co-accessibility and HiChIP. We performed a genome-wide pooled CRISPR loss-of-function screen in EndoC-betaH1 cells, which identified 867 genes affecting cytokine-induced beta cell loss. Genes that promoted beta cell survival and had up-regulated expression in cytokine exposure were specifically enriched at T1D loci, and these genes were preferentially involved in inhibiting inflammatory response, ubiquitin-mediated proteolysis, mitophagy and autophagy. We identified 2,229 variants in cytokine-responsive beta cell cCREs altering transcription factor (TF) binding using high-throughput SNP-SELEX, and variants altering binding of TF families regulating stress, inflammation and apoptosis were broadly enriched for T1D association. Finally, through integration with genetic fine mapping, we annotated T1D loci regulating beta cell survival in cytokine exposure. At the 16p13 locus, a T1D variant affected TF binding in a cytokine-induced beta cell cCRE that physically interacted with the SOCS1 promoter, and increased SOCS1 activity promoted beta cell survival in cytokine exposure. Together our findings reveal processes and genes acting in beta cells during cytokine exposure that intrinsically modulate risk of T1D.

scholarly journals The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Marta Letizia Hribal ◽  
Elettra Mancuso ◽  
Gaetano Paride Arcidiacono ◽  
Annalisa Greco ◽  
Donatella Musca ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Survival ◽  
High Glucose ◽  
Chronic Exposure ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Pleckstrin Homology Domain ◽  
Causative Role

Currently available antidiabetic treatments fail to halt, and may even exacerbate, pancreatic β-cell exhaustion, a key feature of type 2 diabetes pathogenesis; thus, strategies to prevent, or reverse, β-cell failure should be actively sought. The serine threonine kinase Akt has a key role in the regulation of β-cell homeostasis; among Akt modulators, a central role is played by pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family. Here, taking advantage of an in vitro model of chronic exposure to high glucose, we demonstrated that PHLPPs, particularly the second family member called PHLPP2, are implicated in the ability of pancreatic β cells to deal with glucose toxicity. We observed that INS-1 rat pancreatic β cell line maintained for 12–15 passages at high (30 mM) glucose concentrations (INS-1 HG) showed increased expression of PHLPP2 and PHLPP1 both at mRNA and protein level as compared to INS-1 maintained for the same number of passages in the presence of normal glucose levels (INS-1 NG). These changes were paralleled by decreased phosphorylation of Akt and by increased expression of apoptotic and autophagic markers. To investigate if PHLPPs had a casual role in the alteration of INS-1 homeostasis observed upon chronic exposure to high glucose concentrations, we took advantage of shRNA technology to specifically knock-down PHLPPs. We obtained proof-of-concept evidence that modulating PHLPPs expression may help to restore a healthy β cell mass, as the reduced expression of PHLPP2/1 was accompanied by a recovered balance between pro- and antiapoptotic factor levels. In conclusion, our data provide initial support for future studies aimed to identify pharmacological PHLPPs modulator to treat beta-cell survival impairment. They also contribute to shed some light on β-cell dysfunction, a complex and unsatisfactorily characterized phenomenon that has a central causative role in the pathogenesis of type 2 diabetes.

scholarly journals Ubiquitin C-terminal hydrolase L1 is required for pancreatic beta cell survival and function in lipotoxic conditions

Diabetologia ◽  
2011 ◽  
Vol 55 (1) ◽  
pp. 128-140 ◽  
Author(s):  
K. Y. Chu ◽  
H. Li ◽  
K. Wada ◽  
J. D. Johnson
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
And Function

scholarly journals The Investigation of Antidiabetic Effects of Leontice leontopetalum Extract on Human Pancreatic β Cell Lines (1.1B4) Treated with Streptozotocin

2018 ◽  
Vol 6 (6) ◽  
pp. 792
Author(s):  
Celal Güven ◽  
Eylem Taşkın ◽  
Önder Yumrutaş ◽  
Leyla Türker Şener ◽  
Fulya Dal ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
Insulin Content ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Levels ◽  
Dose Dependent ◽  
Antidiabetic Effects

One of the alternative therapeutic methods is herbal medicine. Leontice leontopetalum belongs to Berberidaceae family. The aim of study was investigated the extract of LL on human pancreatic beta cell-treated with STZ. Materials and methods: The human pancreatic beta cell (1.1B4) line was used the current study. LL’s extracts (1, 10, 100, and 1000 ug/ml) were supplemented in media for twenty-four hours and/or after STZ treatment (10 and 20 mM). Cells survivals (MTT), cells proliferation were shown by using xCelligence. Insulin content and releasing were measured at 1.1, 8.4 and 16.7 mM glucose concentrations. Results: The result of MTT was shown that cell survival was decreased, based on dose-dependent. When looked at xCelligence results, cell proliferation in STZ groups and the lowest and highest concentrations of LL were attenuated in a dose-dependent manner. Also, cotreatments of LL and STZ were decreased as well. The result of insulin-releasing on glucose induction was shown that STZ concentration gave rise to reduce insulin content at low and high glucose levels. Also, co-treatment of LL and STZ attenuated insulin content based on dose. Conclusion: It was considered that LL treatment led to increased insulin realizing, resulting from decreasing insulin content in diabetic beta cells, but decrease cell survival.

scholarly journals Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling

2015 ◽  
Vol 400 ◽  
pp. 112-128 ◽  
Author(s):  
Katerina Kapodistria ◽  
Effie-Photini Tsilibary ◽  
Panagiotis Politis ◽  
Petros Moustardas ◽  
Aristidis Charonis ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Transmembrane Protein ◽  
Pancreatic Beta Cell ◽  
Survival Signaling

The Tp53 network regulates pancreatic beta cell survival

2018 ◽  
Author(s):  
N Müller ◽  
C Wessel ◽  
K Grieß ◽  
C Polanski ◽  
BF Belgardt
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell
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