scholarly journals ER Stress as a Trigger for  -Cell Dysfunction and Autoimmunity in Type 1 Diabetes

Diabetes ◽  
2012 ◽  
Vol 61 (4) ◽  
pp. 780-781 ◽  
Author(s):  
B. O'Sullivan-Murphy ◽  
F. Urano
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Cell Dysfunction

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

scholarly journals The role of beta-cell dysfunction in early type 1 diabetes

2020 ◽  
Vol 27 (4) ◽  
pp. 215-224 ◽  
Author(s):  
Emily K. Sims ◽  
Raghavendra G. Mirmira ◽  
Carmella Evans-Molina
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Early Type ◽  
Cell Dysfunction

MicroRNAs in CD4 + T cell subsets are markers of disease risk and T cell dysfunction in individuals at risk for type 1 diabetes

2016 ◽  
Vol 68 ◽  
pp. 52-61 ◽  
Author(s):  
Yuxia Zhang ◽  
Zhi-Ping Feng ◽  
Gaetano Naselli ◽  
Fiona Bell ◽  
James Wettenhall ◽  
...  
Keyword(s):  
At Risk ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Disease Risk ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals Regulatory T cell dysfunction in type 1 diabetes: what’s broken and how can we fix it?

Diabetologia ◽  
2017 ◽  
Vol 60 (10) ◽  
pp. 1839-1850 ◽  
Author(s):  
Caroline M. Hull ◽  
Mark Peakman ◽  
Timothy I. M. Tree
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals Beta Cell Autophagy in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Author(s):  
Charanya Muralidharan ◽  
Amelia K Linnemann
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Potential Role ◽  
Cell Dysfunction ◽  
Unconventional Secretion ◽  
Insulin Dependent

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic beta cells are destroyed resulting in hyperglycemia. This multi-factorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the beta cells may promote a change in the local immune mileu, contributing to autoimmunity. Therefore, many studies have been focused on intrinsic beta cell mechanisms that aid in restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects in which are clearly linked with beta cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards beta cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for beta cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the beta cell and immune cells.

scholarly journals Deletion of the RNLS Gene using CRISPR/Cas9 as Pancreatic Cell β Protection against Autoimmune and ER Stress for Type 1 Diabetes Mellitus

2021 ◽  
Vol 9 (F) ◽  
pp. 613-619
Author(s):  
Aufa Baraja ◽  
Fadhilla Rachmawati Sunarto ◽  
Arga Setyo Adji ◽  
Fitri Handajani ◽  
Firman Suryadi Rahman
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
B Cells ◽  
Er Stress ◽  
Type 1 Diabetes Mellitus ◽  
Genome Editing ◽  
Immune Recognition ◽  
Pancreatic Cell ◽  
The Unfolded Protein Response

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease in children which is usually caused by autoimmunity that damages pancreatic a and b cells which have functions as blood glucose regulators. Some studies stated that Renalase (RNLS) gene deletion will protect these b cells from autoimmune reactions and Endoplasmic Reticulum (ER) stress. RNLS deletion by genome editing Clustered Regular interspersed Short Palindromic Repeats-CRISPR-related (CRISPR/Cas9) is believed to have the potential to be a therapy for T1DM Patients. AIM: This research was conducted to know the potential of RNLS deletion using the CRISPR/Cas9 as an effective therapy and whether it has a permanent effect on T1DM patients. METHODS: The method applied in this research summarized articles by analyzing the titles and abstracts of various predetermined keywords. In this case, the author chose a full-text article published within the past 10 years by prioritizing searches in the last 5 years through PubMed, Google Scholar, Science Direct, Cochrane, American Diabetes Association, and official guidelines from IDAI. RESULTS: RNLS deletion using CRISPR/Cas9 in mice weakened the response of polyclonal -cell-reactive CD8+ T cells and disrupted the immune recognition to cells so that autoimmune killing did occur. In addition, such deletion prevents RNLS ER stress by increasing the threshold, triggering the unfolded protein response so that ER stress is difficult to occur. RNLS mutations in b cells also increase b cell survivability to oxidative stress. CONCLUSION: b cells RNLS deletion by genome editing CRISPR/Cas9 is effective in protecting b cells from autoimmune reactions and RE stress. However, further research is needed to determine the side effects and safety of its use.

scholarly journals β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis

JCI Insight ◽  
2018 ◽  
Vol 3 (15) ◽  
Author(s):  
Carmella Evans-Molina ◽  
Emily K. Sims ◽  
Linda A. DiMeglio ◽  
Heba M. Ismail ◽  
Andrea K. Steck ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Diagnosis ◽  
Β Cell ◽  
Cell Dysfunction

scholarly journals New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Christine Bender ◽  
Sakthi Rajendran ◽  
Matthias G. von Herrath
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cd8 T Cells ◽  
Over Expression ◽  
Cell Dysfunction ◽  
Human Type ◽  
Human Type 1 Diabetes

Since the establishment of the network for pancreatic organ donors with diabetes (nPOD), we have gained unprecedented insight into the pathology of human type 1 diabetes. Many of the pre-existing “dogmas”, mostly derived from studies of animal models and sometimes limited human samples, have to be revised now. For example, we have learned that autoreactive CD8 T cells are present even in healthy individuals within the exocrine pancreas. Furthermore, their “attraction” to islets probably relies on beta-cell intrinsic events, such as the over-expression of MHC class I and resulting presentation of autoantigens such as (prepro)insulin. In addition, we are discovering other signs of beta-cell dysfunction, possibly at least in part due to stress, such as the over-expression of certain cytokines. This review summarizes the latest developments focusing on cytokines and autoreactive CD8 T cells in human type 1 diabetes pathogenesis.

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