scholarly journals Lipid Droplets Protect Human β Cells from Lipotoxic-Induced Stress and Cell Identity Changes

Diabetes ◽  
2021 ◽  
pp. db210261
Author(s):  
Xin Tong ◽  
Roland Stein
Keyword(s):  
Lipid Droplets ◽  
Β Cells ◽  
Cell Identity ◽  
Induced Stress ◽  
Identity Changes

scholarly journals Adaptation to chronic ER stress enforces pancreatic β-cell plasticity

2021 ◽  
Author(s):  
Chien-Wen Chen ◽  
Bo-Jhih Guan ◽  
Mohammed R Alzahrani ◽  
Zhaofeng Gao ◽  
Long Gao ◽  
...  
Keyword(s):  
Er Stress ◽  
Stress Responses ◽  
Cell Function ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Cell Identity ◽  
Β Cell Function ◽  
Novel Biomarkers ◽  
High Degree

Pancreatic β-cells undergo high levels of endoplasmic reticulum (ER) stress due to their role in insulin secretion. Hence, they require sustainable and efficient adaptive stress responses to cope with the stress. Whether duration and episodes of chronic ER stress directly compromises β-cell identity is largely unknown. We show that under reversible, chronic ER stress, β-cells undergo a distinct transcriptional and translational reprogramming. During reprogramming, expression of master regulators of β-cell function and identity and proinsulin processing is impaired. Upon recovery from stress, β-cells regain their identity, highlighting a high-degree of adaptive β-cell plasticity. Remarkably, when stress episodes exceed a certain threshold, β-cell identity is gradually lost. Single cell RNA-seq analysis of islets from type 1 diabetes (T1D) patients, identifies the severe deregulation of the chronic stress-adaptation program, and reveals novel biomarkers for progression of T1D. Our results suggest β-cell adaptive exhaustion (βEAR) is a significant component of the pathogenesis of T1D.

scholarly journals Cellular plasticity at the nexus of development and disease

Development ◽  
2021 ◽  
Vol 148 (3) ◽  
pp. dev197392
Author(s):  
Lillian B. Spatz ◽  
Ramon U. Jin ◽  
Jason C. Mills
Keyword(s):  
Global Health ◽  
Initial Step ◽  
Cell Plasticity ◽  
Cell Identity ◽  
Fields Of Study ◽  
Poster Sessions ◽  
Epigenomic Regulation ◽  
Cellular Identity ◽  
Developmental Contexts ◽  
Identity Changes

ABSTRACTIn October 2020, the Keystone Symposia Global Health Series hosted a Keystone eSymposia entitled ‘Tissue Plasticity: Preservation and Alteration of Cellular Identity’. The event synthesized groundbreaking research from unusually diverse fields of study, presented in various formats, including live and virtual talks, panel discussions and interactive e-poster sessions. The meeting focused on cell identity changes and plasticity in multiple tissues, species and developmental contexts, both in homeostasis and during injury. Here, we review the key themes of the meeting: (1) cell-extrinsic drivers of plasticity; (2) epigenomic regulation of cell plasticity; and (3) conserved mechanisms governing plasticity. A salient take-home conclusion was that there may be conserved mechanisms used by cells to execute plasticity, with autodegradative activity (autophagy and lysosomes) playing a crucial initial step in diverse organs and organisms.

scholarly journals VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress

Diabetes ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2377-2391
Author(s):  
Daisuke Sakano ◽  
Fumiya Uefune ◽  
Hiraku Tokuma ◽  
Yuki Sonoda ◽  
Kumi Matsuura ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Β Cells ◽  
Induced Stress

scholarly journals Adipose Triglyceride Lipase Is a Key Lipase for the Mobilization of Lipid Droplets in Human β-Cells and Critical for the Maintenance of Syntaxin 1a Levels in β-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1178-1192
Author(s):  
Siming Liu ◽  
Joseph A. Promes ◽  
Mikako Harata ◽  
Akansha Mishra ◽  
Samuel B. Stephens ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Adipose Triglyceride Lipase ◽  
Β Cells ◽  
Syntaxin 1A ◽  
Triglyceride Lipase

scholarly journals Epigenetic Regulation of β Cell Identity and Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoqiang Sun ◽  
Liu Wang ◽  
S. M. Bukola Obayomi ◽  
Zong Wei
Keyword(s):  
Dna Methylation ◽  
Histone Modification ◽  
Driving Forces ◽  
Β Cells ◽  
Β Cell ◽  
Cell Identity ◽  
Potential Implication ◽  
Postnatal Maturation ◽  
Cell Dysfunction ◽  
Epigenetic Signatures

β cell dysfunction and failure are driving forces of type 2 diabetes mellitus (T2DM) pathogenesis. Investigating the underlying mechanisms of β cell dysfunction may provide novel targets for the development of next generation therapy for T2DM. Epigenetics is the study of gene expression changes that do not involve DNA sequence changes, including DNA methylation, histone modification, and non-coding RNAs. Specific epigenetic signatures at all levels, including DNA methylation, chromatin accessibility, histone modification, and non-coding RNA, define β cell identity during embryonic development, postnatal maturation, and maintain β cell function at homeostatic states. During progression of T2DM, overnutrition, inflammation, and other types of stress collaboratively disrupt the homeostatic epigenetic signatures in β cells. Dysregulated epigenetic signatures, and the associating transcriptional outputs, lead to the dysfunction and eventual loss of β cells. In this review, we will summarize recent discoveries of the establishment and disruption of β cell-specific epigenetic signatures, and discuss the potential implication in therapeutic development.

scholarly journals A δ-cell subpopulation with a pro-β-cell identity confers efficient age-independent recovery in a zebrafish model of diabetes

2021 ◽  
Author(s):  
Claudio A Carril Pardo ◽  
Laura Massoz ◽  
Marie Dupont ◽  
David Bergemann ◽  
Jordane Bourdouxhe ◽  
...  
Keyword(s):  
Cell Subpopulation ◽  
Diabetic Patients ◽  
Β Cells ◽  
Β Cell ◽  
Zebrafish Model ◽  
Cell Identity ◽  
Pancreatic Cells ◽  
Insulin Cells ◽  
Cell Conversion ◽  
Age Independent

Restoring damaged β-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study β-cells arising following destruction. We show that most new insulin cells differ from the original β-cells as they are Somatostatin+ Insulin+, but are nevertheless functional and normalize glycemia. These bihormonal cells are transcriptionally close to a subset of δ-cells in normal islets characterized by the expression of somatostatin 1.1 (sst1.1), the β-cell genes pdx1, slc2a2 and gck, and the machinery for glucose-induced Insulin secretion. β-cell destruction triggers massive sst1.1 δ-cell conversion to bihormonal cells. Our work shows that their pro- β-cell identity predisposes this zebrafish δ-cell subpopulation to efficient age-independent neogenesis of Insulin-producing cells and provides clues to restoring functional β-cells in mammalian diabetes models.

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 Changes to the identity of EndoC-βH1 beta cells may be mediated by stress-induced depletion of HNRNPD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicola Jeffery ◽  
David Chambers ◽  
Brandon M. Invergo ◽  
Ryan M. Ames ◽  
Lorna W. Harries
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Population ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Potential Candidate ◽  
Cell Identity ◽  
Patients With Diabetes ◽  
Stressed Cells ◽  
Identity Changes

Abstract Background Beta cell identity changes occur in the islets of donors with diabetes, but the molecular basis of this remains unclear. Protecting residual functional beta cells from cell identity changes may be beneficial for patients with diabetes. Results A somatostatin-positive cell population was induced in stressed clonal human EndoC-βH1 beta cells and was isolated using FACS. A transcriptomic characterisation of somatostatin-positive cells was then carried out. Gain of somatostatin-positivity was associated with marked dysregulation of the non-coding genome. Very few coding genes were differentially expressed. Potential candidate effector genes were assessed by targeted gene knockdown. Targeted knockdown of the HNRNPD gene induced the emergence of a somatostatin-positive cell population in clonal EndoC-βH1 beta cells comparable with that we have previously reported in stressed cells. Conclusions We report here a role for the HNRNPD gene in determination of beta cell identity in response to cellular stress. These findings widen our understanding of the role of RNA binding proteins and RNA biology in determining cell identity and may be important for protecting remaining beta cell reserve in diabetes.

scholarly journals Stress-induced adaptive islet cell identity changes

2016 ◽  
Vol 18 ◽  
pp. 87-96 ◽  
Author(s):  
V. Cigliola ◽  
F. Thorel ◽  
S. Chera ◽  
P. L. Herrera
Keyword(s):  
Islet Cell ◽  
Cell Identity ◽  
Identity Changes

scholarly journals Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

2010 ◽  
Vol 9 (1) ◽  
pp. 108 ◽  
Author(s):  
Kristofer Thörn ◽  
Meri Hovsepyan ◽  
Peter Bergsten
Keyword(s):  
Β Cells ◽  
Induced Stress
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