2184-P: Foxo1-CoF Repressor (FCoR) Regulates Pancreatic Alpha- and Beta-Cell Identity by both DNA and Histone Methylation

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2184-P
Author(s):  
NORIKO KODANI ◽  
MASAKI KOBAYASHI ◽  
OSAMU KIKUCHI ◽  
TADAHIRO KITAMURA ◽  
HIROSHI ITOH ◽  
...  
Keyword(s):  
Beta Cell ◽  
Histone Methylation ◽  
Cell Identity

176-OR: STIM1 Deletion Leads to Loss of Beta-Cell Identity in High-Fat Diet-Fed Female Mice

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 176-OR
Author(s):  
PAUL SOHN ◽  
PREETHI KRISHNAN ◽  
CHIH-CHUN LEE ◽  
TATSUYOSHI KONO ◽  
CARMELLA EVANS-MOLINA
Keyword(s):  
Beta Cell ◽  
High Fat Diet ◽  
High Fat ◽  
Cell Identity ◽  
Female Mice

scholarly journals Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 395-409 ◽  
Author(s):  
Masaya Oshima ◽  
Séverine Pechberty ◽  
Lara Bellini ◽  
Sven O. Göpel ◽  
Mélanie Campana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Identity ◽  
Human Beta Cells ◽  
Human Beta Cell ◽  
Stearoyl Coa Desaturase

Abstract Aims/hypothesis During the onset of type 2 diabetes, excessive dietary intake of saturated NEFA and fructose lead to impaired insulin production and secretion by insulin-producing pancreatic beta cells. The majority of data on the deleterious effects of lipids on functional beta cell mass were obtained either in vivo in rodent models or in vitro using rodent islets and beta cell lines. Translating data from rodent to human beta cells remains challenging. Here, we used the human beta cell line EndoC-βH1 and analysed its sensitivity to a lipotoxic and glucolipotoxic (high palmitate with or without high glucose) insult, as a way to model human beta cells in a type 2 diabetes environment. Methods EndoC-βH1 cells were exposed to palmitate after knockdown of genes related to saturated NEFA metabolism. We analysed whether and how palmitate induces apoptosis, stress and inflammation and modulates beta cell identity. Results EndoC-βH1 cells were insensitive to the deleterious effects of saturated NEFA (palmitate and stearate) unless stearoyl CoA desaturase (SCD) was silenced. SCD was abundantly expressed in EndoC-βH1 cells, as well as in human islets and human induced pluripotent stem cell-derived beta cells. SCD silencing induced markers of inflammation and endoplasmic reticulum stress and also IAPP mRNA. Treatment with the SCD products oleate or palmitoleate reversed inflammation and endoplasmic reticulum stress. Upon SCD knockdown, palmitate induced expression of dedifferentiation markers such as SOX9, MYC and HES1. Interestingly, SCD knockdown by itself disrupted beta cell identity with a decrease in mature beta cell markers INS, MAFA and SLC30A8 and decreased insulin content and glucose-stimulated insulin secretion. Conclusions/interpretation The present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity. Data availability Microarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code.

scholarly journals Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes

2019 ◽  
Vol 19 (9) ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Alexandra E. Butler
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Identity

scholarly journals OR05-3 Mir-21 Contributes to Cytokine-Induced Beta Cell Dysfunction via Inhibition of mRNAs Regulating Beta Cell Identity

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sara Ibrahim ◽  
Ryan Anderson ◽  
Raghavendra Mirmira ◽  
Emily Sims
Keyword(s):  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Cell Identity ◽  
Cell Dysfunction

PS18 - 3. Loss of beta-cell identity occurs in type 2 diabetes and is associated with islet amyloid depositions

2013 ◽  
Vol 11 (4) ◽  
pp. 201-201
Author(s):  
H. Siebe Spijker ◽  
Heein Song ◽  
Anne Clark ◽  
Marten Engelse ◽  
Ton J. Rabelink ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Islet Amyloid ◽  
Cell Identity

scholarly journals EndoC-βH1 multi-genomic profiling defines gene regulatory programs governing human pancreatic β cell identity and function

2018 ◽  
Author(s):  
Nathan Lawlor ◽  
Eladio J. Márquez ◽  
Peter Orchard ◽  
Narisu Narisu ◽  
Muhammad Saad Shamim ◽  
...  
Keyword(s):  
Beta Cell ◽  
Web Application ◽  
Regulatory Networks ◽  
Cell Function ◽  
Cell Model ◽  
Regulatory Element ◽  
Human Islets ◽  
Chromatin Interaction ◽  
Cell Identity ◽  
Molecular Landscape

SUMMARYEndoC-βH1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of beta cell function, especially in the context of diabetes. Comprehensive knowledge of its molecular landscape is lacking yet required to fully take advantage of this model. Here, we report extensive chromosomal (spectral karyotyping), genetic (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), and transcriptomic (RNA-seq, miRNA-seq) maps of this cell model. Integrated analyses of these maps define known (e.g.,PDX1, ISL1) and putative (e.g.,PCSK1, mir-375) beta cell-specific chromatin interactions and transcriptionalcis-regulatory networks, and identify allelic effects oncis-regulatory element use and expression.Importantly, comparative analyses with maps generated in primary human islets/beta cells indicate substantial preservation of chromatin looping, but also highlight chromosomal heterogeneity and fetal genomic signatures in EndoC-βH1. Together, these maps, and an interactive web application we have created for their exploration, provide important tools for the broad community in the design and success of experiments to probe and manipulate the genetic programs governing beta cell identity and (dys)function in diabetes.

scholarly journals Beta cell identity changes with mild hyperglycemia: Implications for function, growth, and vulnerability

2020 ◽  
Vol 35 ◽  
pp. 100959 ◽  
Author(s):  
Aref G. Ebrahimi ◽  
Jennifer Hollister-Lock ◽  
Brooke A. Sullivan ◽  
Ryohei Tsuchida ◽  
Susan Bonner-Weir ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Identity ◽  
Mild Hyperglycemia ◽  
Identity Changes

scholarly journals Methionine metabolism influences the genomic architecture of H3K4me3 with the link to gene expression encoded in peak width

2018 ◽  
Author(s):  
Ziwei Dai ◽  
Samantha J. Mentch ◽  
Xia Gao ◽  
Sailendra N. Nichenametla ◽  
Jason W. Locasale
Keyword(s):  
Gene Expression ◽  
Nutrient Availability ◽  
Histone Methylation ◽  
Human Cancer ◽  
Peak Width ◽  
Cell Identity ◽  
Chromatin Dynamics ◽  
Human Cancer Cells ◽  
Genomic Architecture ◽  
Almost All

AbstractNutrition and metabolism are known to influence chromatin biology and epigenetics by modifying the levels of post-translational modifications on histones, yet how changes in nutrient availability influence specific aspects of genomic architecture and connect to gene expression is unknown. To investigate this question we considered, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyzed the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability under conditions that are known to affect the global levels of histone methylation in both normal rodent physiology and in human cancer cells. Surprisingly, we found that the location of H3K4me3 peaks at specific genomic loci was largely preserved under conditions of methionine restriction. However, upon examining different geometrical features of peak shape, it was found that the response of H3K4me3 peak width encoded almost all aspects of H3K4me3 biology including changes in expression levels, and the presence of cell identity and cancer associated genes. These findings reveal simple yet new and profound principles for how nutrient availability modulates specific aspects of chromatin dynamics to mediate key biological features.

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