scholarly journals Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails Markers of β-Cell Dedifferentiation in db/db Mice

Diabetes ◽  
2017 ◽  
Vol 66 (8) ◽  
pp. 2092-2101 ◽  
Author(s):  
Emi Ishida ◽  
Ja Young Kim-Muller ◽  
Domenico Accili
Keyword(s):  
Β Cell ◽  
Cell Dedifferentiation ◽  
Rosiglitazone Treatment

Mscs Ameliorate β Cell Dysfunction of Human T2DM Islets by Reversing β Cell Dedifferentiation

2019 ◽  
Author(s):  
Le Wang ◽  
Tengli Liu ◽  
Rui Liang ◽  
Guanqiao Wang ◽  
Yaojuan Liu ◽  
...  
Keyword(s):  
Β Cell ◽  
Cell Dedifferentiation ◽  
Cell Dysfunction

Paraneoplastic β Cell Dedifferentiation in Nondiabetic Patients with Pancreatic Cancer

2019 ◽  
Vol 105 (4) ◽  
pp. e1489-e1503 ◽  
Author(s):  
Yichen Wang ◽  
Qicheng Ni ◽  
Jiajun Sun ◽  
Min Xu ◽  
Jing Xie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endocrine Cells ◽  
Fasting Blood Glucose ◽  
Ductal Adenocarcinoma ◽  
Benign Tumors ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Glucose Transporter 2 ◽  
Onset Diabetes ◽  
New Onset

Abstract Context Beta-cell dedifferentiation was recently proposed as a mechanism of β-cell dysfunction, but whether it can be a trigger of β-cell failure preceding hyperglycemia in humans is uncertain. Pancreatic cancer can cause new-onset diabetes, yet the underlying mechanism is unknown. Objective To investigate whether β-cell dedifferentiation is present in nondiabetic pancreatic ductal adenocarcinoma (PDAC) patients, we examined pancreatic islets from 15 nondiabetic patients with benign tumors (control) and 15 nondiabetic PDAC patients. Design We calculated the number of hormone-negative endocrine cells and evaluated important markers of β-cell dedifferentiation and function in the paraneoplastic islets. We assessed tumor-related inflammatory changes under the pancreatic cancer microenvironment and their influence on β-cell identity. Results We found nearly 10% of nonhormone expressing endocrine cells in nondiabetic PDAC subjects. The PDAC islets were dysfunctional, evidenced by low expression of Glucose transporter 2 (GLUT2) and Urocortin3 (UCN3), and concomitant upregulation of Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) expression and proinsulin accumulation. Pancreatic cancer caused paraneoplastic inflammation with enhanced tissue fibrosis, monocytes/macrophages infiltration, and elevated inflammatory cytokines. Moreover, we detected β-cell dedifferentiation and defects in GSIS in islets exposed to PANC-1 (a cell line established from a pancreatic carcinoma of ductal origin from a 56-year-old Caucasian male)-conditioned medium. In a larger cohort, we showed high prevalence of new-onset diabetes in PDAC subjects, and fasting blood glucose (FBG) was found to be an additional useful parameter for early diagnosis of PDAC. Conclusions Our data provide a rationale for β-cell dedifferentiation in the pathogenesis of pancreatic cancer–associated diabetes. We propose that β-cell dedifferentiation can be a trigger for β-cell failure in humans, before hyperglycemia occurs.

scholarly journals ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation

2015 ◽  
Vol 36 (5) ◽  
pp. 756-764 ◽  
Author(s):  
Doriane Ripoche ◽  
Jérémie Charbord ◽  
Ana Hennino ◽  
Romain Teinturier ◽  
Rémy Bonnavion ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mutant Mice ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Insulin Expression ◽  
Tumor Plasticity

Loss of pancreatic β-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote β-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor β (TGF-β)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and β-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed β-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor β-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of β-cell maturity, islet plasticity, and progression of insulinoma through its participation in β-cell dedifferentiation.

scholarly journals Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes

2016 ◽  
Vol 101 (3) ◽  
pp. 1044-1054 ◽  
Author(s):  
Francesca Cinti ◽  
Ryotaro Bouchi ◽  
Ja Young Kim-Muller ◽  
Yoshiaki Ohmura ◽  
P. R. Sandoval ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Human Type

scholarly journals The Role of Inflammation in β-cell Dedifferentiation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Thierry M. Nordmann ◽  
Erez Dror ◽  
Friederike Schulze ◽  
Shuyang Traub ◽  
Ekaterine Berishvili ◽  
...  
Keyword(s):  
Β Cell ◽  
Cell Dedifferentiation

scholarly journals Targeting β-cell dedifferentiation and transdifferentiation: opportunities and challenges

2021 ◽  
Author(s):  
Wenrui Wang ◽  
Chuan Zhang
Keyword(s):  
Cell Injury ◽  
Cell Mass ◽  
Treatment Strategies ◽  
Cell Types ◽  
Therapeutic Window ◽  
Time Interval ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Genetically Engineer

The most distinctive pathological characteristics of diabetes mellitus induced by various stressors or immune-mediated injuries are reductions of pancreatic islet β-cell populations and activity. Existing treatment strategies cannot slow disease progression; consequently, research to genetically engineer β-cell-mimetics through bi-directional plasticity is ongoing. The current consensus implicates β cell dedifferentiation as the primary etiology of reduced β-cell mass and activity. This review aims to summarize the etiology and proposed mechanisms of β-cell dedifferentiation, and to explore the possibility that there might be a time interval from the onset of β-cell dysfunction caused by dedifferentiation to the development of diabetes, which may offer a therapeutic window to reduce β-cell injury and to stabilize functionality. In addition, to investigate β-cell plasticity, we review strategies for β-cell regeneration utilizing genetic programming, small molecules, cytokines, and bioengineering to transdifferentiate other cell types into β-cells; and the development of biomimetic acellular constructs to generate fully functional β-cell mimetics. However, the maturation of regenerated β-cells is currently limited. Further studies are needed to develop simple and efficient reprogramming methods for assembling perfectly functional β-cells. Future investigations are necessary to transform diabetes into a potentially curable disease.

scholarly journals Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D

2020 ◽  
Vol 42 ◽  
pp. 101057 ◽  
Author(s):  
Dana Avrahami ◽  
Yue J. Wang ◽  
Jonathan Schug ◽  
Eseye Feleke ◽  
Long Gao ◽  
...  
Keyword(s):  
Single Cell ◽  
Molecular Basis ◽  
Human Islet ◽  
Β Cell ◽  
Cell Dedifferentiation ◽  
Islet Ontogeny
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