scholarly journals MDA5 and PTPN2, two candidate genes for type 1 diabetes, modify pancreatic β-cell responses to the viral by-product double-stranded RNA

2009 ◽  
Vol 19 (1) ◽  
pp. 135-146 ◽  
Author(s):  
Maikel L. Colli ◽  
Fabrice Moore ◽  
Esteban N. Gurzov ◽  
Fernanda Ortis ◽  
Decio L. Eizirik
Keyword(s):  
Type 1 Diabetes ◽  
Candidate Genes ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Double Stranded Rna ◽  
Cell Responses

scholarly journals Nonlinear Analysis for a Type-1 Diabetes Model with Focus on T-Cells and Pancreatic β-Cells Behavior

2020 ◽  
Vol 25 (2) ◽  
pp. 23
Author(s):  
Diana Gamboa ◽  
Carlos E. Vázquez ◽  
Paul J. Campos
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cell Population ◽  
Closed Loop ◽  
Pancreatic Β Cell ◽  
Activated Macrophages ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Type-1 diabetes mellitus (T1DM) is an autoimmune disease that has an impact on mortality due to the destruction of insulin-producing pancreatic β -cells in the islets of Langerhans. Over the past few years, the interest in analyzing this type of disease, either in a biological or mathematical sense, has relied on the search for a treatment that guarantees full control of glucose levels. Mathematical models inspired by natural phenomena, are proposed under the prey–predator scheme. T1DM fits in this scheme due to the complicated relationship between pancreatic β -cell population growth and leukocyte population growth via the immune response. In this scenario, β -cells represent the prey, and leukocytes the predator. This paper studies the global dynamics of T1DM reported by Magombedze et al. in 2010. This model describes the interaction of resting macrophages, activated macrophages, antigen cells, autolytic T-cells, and β -cells. Therefore, the localization of compact invariant sets is applied to provide a bounded positive invariant domain in which one can ensure that once the dynamics of the T1DM enter into this domain, they will remain bounded with a maximum and minimum value. Furthermore, we analyzed this model in a closed-loop scenario based on nonlinear control theory, and proposed bases for possible control inputs, complementing the model with them. These entries are based on the existing relationship between cell–cell interaction and the role that they play in the unchaining of a diabetic condition. The closed-loop analysis aims to give a deeper understanding of the impact of autolytic T-cells and the nature of the β -cell population interaction with the innate immune system response. This analysis strengthens the proposal, providing a system free of this illness—that is, a condition wherein the pancreatic β -cell population holds and there are no antigen cells labeled by the activated macrophages.

scholarly journals Dendritic Cell-Directed CTLA-4 Engagement during Pancreatic β Cell Antigen Presentation Delays Type 1 Diabetes

2010 ◽  
Vol 184 (12) ◽  
pp. 6695-6708 ◽  
Author(s):  
Subha Karumuthil-Melethil ◽  
Nicolas Perez ◽  
Ruobing Li ◽  
Bellur S. Prabhakar ◽  
Mark J. Holterman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Dendritic Cell ◽  
Antigen Presentation ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Antigen

scholarly journals Manganese-Enhanced Magnetic Resonance Imaging Detects Declining Pancreatic β-Cell Mass in a Cyclophosphamide-Accelerated Mouse Model of Type 1 Diabetes

Diabetes ◽  
2012 ◽  
Vol 62 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Patrick F. Antkowiak ◽  
Brian K. Stevens ◽  
Craig S. Nunemaker ◽  
Marcia McDuffie ◽  
Frederick H. Epstein
Keyword(s):  
Magnetic Resonance Imaging ◽  
Type 1 Diabetes ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Resonance Imaging ◽  
Β Cell

scholarly journals Potential Mimicry of Viral and Pancreatic β Cell Antigens Through Non-Spliced and cis-Spliced Zwitter Epitope Candidates in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Michele Mishto ◽  
Artem Mansurkhodzhaev ◽  
Teresa Rodriguez-Calvo ◽  
Juliane Liepe
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Hla Class I ◽  
Class I ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Increasing evidence suggests that post-translational peptide splicing can play a role in the immune response under pathological conditions. This seems to be particularly relevant in Type 1 Diabetes (T1D) since post-translationally spliced epitopes derived from T1D-associated antigens have been identified among those peptides bound to Human Leucocyte Antigen (HLA) class I and II complexes. Their immunogenicity has been confirmed through CD4+ and CD8+ T cell-mediated responses in T1D patients. Spliced peptides theoretically have a large sequence variability. This might increase the frequency of viral-human zwitter peptides, i.e. peptides that share a complete sequence homology irrespective of whether they originate from human or viral antigens, thereby impinging upon the discrimination between self and non-self antigens by T cells. This might increase the risk of autoimmune responses triggered by viral infections. Since enteroviruses and other viral infections have historically been associated with T1D, we investigated whether cis-spliced peptides derived from selected viruses might be able to trigger CD8+ T cell-mediated autoimmunity. We computed in silico viral-human non-spliced and cis-spliced zwitter epitope candidates, and prioritized peptide candidates based on: (i) their binding affinity to HLA class I complexes, (ii) human pancreatic β cell and medullary thymic epithelial cell (mTEC) antigens’ mRNA expression, (iii) antigen association with T1D, and (iv) potential hotspot regions in those antigens. Neglecting potential T cell receptor (TCR) degeneracy, no viral-human zwitter non-spliced peptide was found to be an optimal candidate to trigger a virus-induced CD8+ T cell response against human pancreatic β cells. Conversely, we identified some zwitter peptide candidates, which may be produced by proteasome-catalyzed peptide splicing, and might increase the likelihood of pancreatic β cells recognition by virus-specific CD8+ T cell clones, therefore promoting β cell destruction in the context of viral infections.

Exercise increases pancreatic β‐cell viability in a model of type 1 diabetes through IL‐6 signaling

2015 ◽  
Vol 29 (5) ◽  
pp. 1805-1816 ◽  
Author(s):  
Flavia M. M. Paula ◽  
Nayara C. Leite ◽  
Emerielle C. Vanzela ◽  
Mirian A. Kurauti ◽  
Ricardo Freitas‐Dias ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Viability ◽  
Pancreatic Β Cell ◽  
Β Cell

Pancreatic β-cell Function Is Associated with Augmented Counterregulation to In-Exercise Hypoglycemia in Type 1 Diabetes

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Olivia McCarthy ◽  
Jason Pitt ◽  
Max L. Eckstein ◽  
Othmar Moser ◽  
Stephen C. Bain ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Vitamin D supplementation induces CatG-mediated CD4+ T cell inactivation and restores pancreatic beta-cell function in mice with type 1 diabetes

2021 ◽  
Author(s):  
Xiaoyang Lai ◽  
Xuyang Liu ◽  
Xia Cai ◽  
Fang Zou
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Type 1 diabetes (T1D) is a chronic autoimmune disease accompanied by the immune-mediated destruction of pancreatic β-cells. In this study, we aimed to explore the regulatory effects of Vitamin D (VD) supplementation on pancreatic β-cell function by altering the expression of bioinformatically identified cathepsin G (CatG) in T1D model mice. A T1D mouse model was established in non-obese diabetic (NOD) mice, and their islets were isolated and purified. Pancreatic mononuclear cells (MNCs) were collected, from which CD4+ T cells were isolated. The levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) in the supernatant of mouse pancreatic tissue homogenate were assessed using ELISA. Immunohistochemistry and TUNEL staining were conducted to evaluate the effects of VD supplementation on pancreatic tissues of T1D mice. The pancreatic beta-cell line MIN6 was used for in vitro substantiation of findings in vivo. VD supplementation reduced glucose levels and improved glucose tolerance in T1D mice. Further, VD supplementation improved pancreatic β-cell function and suppressed immunological and inflammatory reactions in the T1D mice. We documented overexpression of CatG in diabetes tissue samples, and then showed that VD supplementation normalized the islet immune microenvironment through down-regulating CatG expression in T1D mice. Experiments in vitro subsequently demonstrated that VD supplementation impeded CD4+ T activation by down-regulating CatG expression, and thereby enhanced pancreatic β-cell function. Results of the present study elucidated that VD supplementation can down-regulate the expression of CatG and inhibit CD4+ T cell activation, thereby improving β-cell function in T1D.

Type 1 Diabetic Serum Interferes with Pancreatic β-cell Ca2+ -Handling

2007 ◽  
Vol 27 (6) ◽  
pp. 321-326 ◽  
Author(s):  
N. Dekki ◽  
R. Nilsson ◽  
S. Norgren ◽  
S. M. Rössner ◽  
I. Appelskog ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Ethnic Background ◽  
Diabetic Patients ◽  
Pancreatic Β Cell ◽  
Newly Diagnosed ◽  
Β Cells ◽  
Β Cell ◽  
First Degree Relatives ◽  
Type 1 Diabetic Patients

The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic β-cell cytoplasmic free Ca2+ concentration, [Ca2+]i, and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca2+]i, upon depolarization, were measured in β-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic β-cell Ca2+-handling. This effect on β-cell [Ca2+]i could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca2+-handling may aggravate development of β-cell destruction.

scholarly journals B-Lymphocytes Expressing an Ig Specificity Recognizing the Pancreatic β-Cell Autoantigen Peripherin Are Potent Contributors to Type 1 Diabetes Development in NOD Mice

Diabetes ◽  
2016 ◽  
Vol 65 (7) ◽  
pp. 1977-1987 ◽  
Author(s):  
Caroline M. Leeth ◽  
Jeremy Racine ◽  
Harold D. Chapman ◽  
Berta Arpa ◽  
Jorge Carrillo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
B Lymphocytes ◽  
Nod Mice ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Diabetes Development
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