Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Cellular and Molecular Biology of the Beta Cell
share announcement

Cellular and Molecular Biology of the Beta Cell

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 23102

Special Issue Editor

Dr. Jean Sébastien Annicotte

E-Mail Website1 Website2
Guest Editor
Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 – RID-AGE-Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000 Lille, France
Interests: pancreatic beta cell; metabolic homeostasis; type 2 diabetes; insulin secretion; insulin resistance; epigenetic regulations; cell cycle regulators
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glucose metabolism is regulated physiologically through a feedback loop between insulin-producing pancreatic β-cells and insulin-sensitive tissues (i.e., liver, muscle or adipose tissues), in which tissue sensitivity to insulin correlates with the magnitude of the β-cell response. Type 2 Diabetes (T2D) is characterized by high blood glucose levels and develops due to inadequate pancreatic β-cell function (i.e., insulin secretion) in the face of peripheral insulin resistance. In the context of T2D research, genome-wide association studies, as well as postmortem studies of diabetic patients’ pancreas specimens, have revealed that β-cell dysfunction is thought to have a major role in the pathogenesis of T2D. The restoration of normal β-cell mass and function has therefore become a field of intensive research seeking the next generation of antidiabetic drugs.

Metabolic (dys)homeostasis is controlled by fine-tuned and non-permanent modulations of gene expression in response to extracellular stimuli. This allows the cells to adapt to their environment to maintain cell integrity in response to metabolic challenges. Among the factors that impact the disease, obesity, physical inactivity, and aging are considered non-genetic risk factors contributing to T2D development. These environmental factors have been reported to shape subtle and reversible cellular and molecular events, including, but not limited to, modifications of DNA, named epigenetic regulations, influencing gene transcription and organ dysfunction. Although the mechanisms underlying β-cell dysfunction are still debated, emerging data suggest that specific molecular and cellular effects are necessary for β-cell adaptation to metabolic stress.

The aim of this Special Issue is to provide an overview of the recent molecular and cellular cues involved in the control of β-cell mass and/or function and propose an integrated view of the biological effects that could contribute at the β-cell level to metabolic disorders, such as T2D. This Special Issue welcomes mechanistic studies investigating the loss of β-cell mass and/or function in the context of T2D. We hope that the original research and reviews presented by expert laboratories will be valuable to improve our knowledge of the fascinating β-cell and provide new concepts to prevent or propose new treatment strategies to counteract β-cell failure.

Dr. Jean Sébastien Annicotte
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pancreatic beta cells
  • type 2 diabetes
  • insulin secretion
  • beta cell adaptation
  • beta cell mass
  • beta cell omics

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

18 pages, 3372 KiB  
Article
Loss of Human Beta Cell Identity in a Reconstructed Omental Stromal Cell Environment
by Blandine Secco, Kevin Saitoski, Karima Drareni, Antoine Soprani, Severine Pechberty, Latif Rachdi, Nicolas Venteclef and Raphaël Scharfmann
Cells 2022, 11(6), 924; https://doi.org/10.3390/cells11060924 - 8 Mar 2022
Cited by 1 | Viewed by 2438
Abstract
In human type 2 diabetes, adipose tissue plays an important role in disturbing glucose homeostasis by secreting factors that affect the function of cells and tissues throughout the body, including insulin-producing pancreatic beta cells. We aimed here at studying the paracrine effect of [...] Read more.
In human type 2 diabetes, adipose tissue plays an important role in disturbing glucose homeostasis by secreting factors that affect the function of cells and tissues throughout the body, including insulin-producing pancreatic beta cells. We aimed here at studying the paracrine effect of stromal cells isolated from subcutaneous and omental adipose tissue on human beta cells. We developed an in vitro model wherein the functional human beta cell line EndoC-βH1 was treated with conditioned media from human adipose tissues. By using RNA-sequencing and western blotting, we determined that a conditioned medium derived from omental stromal cells stimulates several pathways, such as STAT, SMAD and RELA, in EndoC-βH1 cells. We also observed that upon treatment, the expression of beta cell markers decreased while dedifferentiation markers increased. Loss-of-function experiments that efficiently blocked specific signaling pathways did not reverse dedifferentiation, suggesting the implication of more than one pathway in this regulatory process. Taken together, we demonstrate that soluble factors derived from stromal cells isolated from human omental adipose tissue signal human beta cells and modulate their identity. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Figure 1

20 pages, 4752 KiB  
Article
Glucose Regulates m6A Methylation of RNA in Pancreatic Islets
by Florine Bornaque, Clément Philippe Delannoy, Emilie Courty, Nabil Rabhi, Charlène Carney, Laure Rolland, Maeva Moreno, Xavier Gromada, Cyril Bourouh, Pauline Petit, Emmanuelle Durand, François Pattou, Julie Kerr-Conte, Philippe Froguel, Amélie Bonnefond, Frédérik Oger and Jean-Sébastien Annicotte
Cells 2022, 11(2), 291; https://doi.org/10.3390/cells11020291 - 15 Jan 2022
Cited by 18 | Viewed by 4147
Abstract
Type 2 diabetes is characterized by chronic hyperglycemia associated with impaired insulin action and secretion. Although the heritability of type 2 diabetes is high, the environment, including blood components, could play a major role in the development of the disease. Amongst environmental effects, [...] Read more.
Type 2 diabetes is characterized by chronic hyperglycemia associated with impaired insulin action and secretion. Although the heritability of type 2 diabetes is high, the environment, including blood components, could play a major role in the development of the disease. Amongst environmental effects, epitranscriptomic modifications have been recently shown to affect gene expression and glucose homeostasis. The epitranscriptome is characterized by reversible chemical changes in RNA, with one of the most prevalent being the m6A methylation of RNA. Since pancreatic β cells fine tune glucose levels and play a major role in type 2 diabetes physiopathology, we hypothesized that the environment, through variations in blood glucose or blood free fatty acid concentrations, could induce changes in m6A methylation of RNAs in pancreatic β cells. Here we observe a significant decrease in m6A methylation upon high glucose concentration, both in mice and human islets, associated with altered expression levels of m6A demethylases. In addition, the use of siRNA and/or specific inhibitors against selected m6A enzymes demonstrate that these enzymes modulate the expression of genes involved in pancreatic β-cell identity and glucose-stimulated insulin secretion. Our data suggest that environmental variations, such as glucose, control m6A methylation in pancreatic β cells, playing a key role in the control of gene expression and pancreatic β-cell functions. Our results highlight novel causes and new mechanisms potentially involved in type 2 diabetes physiopathology and may contribute to a better understanding of the etiology of this disease. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Figure 1

20 pages, 2914 KiB  
Article
Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress
by Nathalie Groen, Floris Leenders, Ahmed Mahfouz, Amadeo Munoz-Garcia, Mauro J. Muraro, Natascha de Graaf, Ton. J. Rabelink, Rob Hoeben, Alexander van Oudenaarden, Arnaud Zaldumbide, Marcel J. T. Reinders, Eelco J. P. de Koning and Françoise Carlotti
Cells 2021, 10(12), 3585; https://doi.org/10.3390/cells10123585 - 19 Dec 2021
Cited by 5 | Viewed by 4072
Abstract
The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process [...] Read more.
The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Figure 1

20 pages, 10808 KiB  
Article
Gfi1 Loss Protects against Two Models of Induced Diabetes
by Tiziana Napolitano, Fabio Avolio, Serena Silvano, Sara Forcisi, Anja Pfeifer, Andhira Vieira, Sergi Navarro-Sanz, Marika Elsa Friano, Chaïma Ayachi, Anna Garrido-Utrilla, Josipa Atlija, Biljana Hadzic, Jérôme Becam, Anette Sousa-De-Veiga, Magali Dodille Plaisant, Shruti Balaji, Didier F. Pisani, Magali Mondin, Philippe Schmitt-Kopplin, Ez-Zoubir Amri and Patrick Collombatadd Show full author list remove Hide full author list
Cells 2021, 10(11), 2805; https://doi.org/10.3390/cells10112805 - 20 Oct 2021
Cited by 3 | Viewed by 3435
Abstract
Background: Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity [...] Read more.
Background: Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity and specification is still elusive. Methods: In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for Gfi1 specifically in the pancreas. Gfi1 conditional knockout animals were phenotypically characterized by immunohistochemistry, RT-qPCR, and RNA scope. To assess the role of Gfi1 in the pathogenesis of diabetes, we challenged Gfi1-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. Results: Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic amylase expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, Gfi1-deficient mice were found resistant to diet-induced hyperglycemia, appearing normoglycemic even after long-term high-fat/high-sugar diet. Another feature observed in mutant acinar cells was the misexpression of ghrelin, a hormone previously suggested to exhibit anti-apoptotic effects on β-cells in vitro. Impressively, Gfi1 mutant mice were found to be resistant to the cytotoxic and diabetogenic effects of high-dose streptozotocin administrations, displaying a negligible loss of β-cells and an imperturbable normoglycemia. Conclusions: Together, these results demonstrate that Gfi1 could turn to be extremely valuable for the development of new therapies and could thus open new research avenues in the context of diabetes research. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Graphical abstract

24 pages, 10372 KiB  
Article
DYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis
by Agata Barzowska, Barbara Pucelik, Katarzyna Pustelny, Alex Matsuda, Alicja Martyniak, Jacek Stępniewski, Anna Maksymiuk, Maciej Dawidowski, Ulli Rothweiler, Józef Dulak, Grzegorz Dubin and Anna Czarna
Cells 2021, 10(9), 2263; https://doi.org/10.3390/cells10092263 - 31 Aug 2021
Cited by 13 | Viewed by 5043
Abstract
The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and [...] Read more.
The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes β-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSC-derived β-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing β-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small–molecule–induced human β-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Figure 1

13 pages, 6010 KiB  
Article
Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus
by Yuko Okano, Atsuro Takeshita, Taro Yasuma, Masaaki Toda, Kota Nishihama, Valeria Fridman D’Alessandro, Chisa Inoue, Corina N. D’Alessandro-Gabazza, Tetsu Kobayashi, Yutaka Yano and Esteban C. Gabazza
Cells 2021, 10(9), 2237; https://doi.org/10.3390/cells10092237 - 29 Aug 2021
Cited by 5 | Viewed by 2666
Abstract
Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the progressive loss of functional β-cells. However, there [...] Read more.
Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the progressive loss of functional β-cells. However, there are currently no available antiapoptotic drugs for diabetes mellitus. This study evaluated whether recombinant human thrombomodulin can inhibit β-cell apoptosis and improve glucose intolerance in a diabetes mouse model. A streptozotocin-induced diabetes mouse model was prepared and treated with thrombomodulin or saline three times per week for eight weeks. The glucose tolerance and apoptosis of β-cells were evaluated. Diabetic mice treated with recombinant human thrombomodulin showed significantly improved glucose tolerance, increased insulin secretion, decreased pancreatic islet areas of apoptotic β-cells, and enhanced proportion of regulatory T cells and tolerogenic dendritic cells in the spleen compared to counterpart diseased mice treated with saline. Non-diabetic mice showed no changes. This study shows that recombinant human thrombomodulin, a drug currently used to treat patients with coagulopathy in Japan, ameliorates glucose intolerance by protecting pancreatic islet β-cells from apoptosis and modulating the immune response in diabetic mice. This observation points to recombinant human thrombomodulin as a promising antiapoptotic drug for diabetes mellitus. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop