scholarly journals The Role of Endoplasmic Reticulum Stress in Autoimmune-Mediated Beta-Cell Destruction in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jixin Zhong ◽  
Xiaoquan Rao ◽  
Jun-Fa Xu ◽  
Ping Yang ◽  
Cong-Yi Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Er Stress ◽  
Autoimmune Response ◽  
Potential Implication ◽  
Beta Cell Destruction ◽  
Cell Destruction

Unlike type 2 diabetes which is caused by the loss of insulin sensitivity, type 1 diabetes (T1D) is manifested by the absolute deficiency of insulin secretion due to the loss ofβmass by autoimmune response againstβ-cell self-antigens. Although significant advancement has been made in understanding the pathoetiology for type 1 diabetes, the exact mechanisms underlying autoimmune-mediatedβ-cell destruction, however, are yet to be fully addressed. Accumulated evidence demonstrates that endoplasmic reticulum (ER) stress plays an essential role in autoimmune-mediatedβ-cell destruction. There is also evidence supporting that ER stress regulates the functionality of immune cells relevant to autoimmune progression during T1D development. In this paper, we intend to address the role of ER stress in autoimmune-mediatedβ-cell destruction during the course of type 1 diabetes. The potential implication of ER stress in modulating autoimmune response will be also discussed. We will further dissect the possible pathways implicated in the induction of ER stress and summarize the potential mechanisms underlying ER stress for mediation ofβ-cell destruction. A better understanding of the role for ER stress in T1D pathoetiology would have great potential aimed at developing effective therapeutic approaches for the prevention/intervention of this devastating disorder.

scholarly journals Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Saurabh Vig ◽  
Joost M. Lambooij ◽  
Arnaud Zaldumbide ◽  
Bruno Guigas
Keyword(s):  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Destruction ◽  
Unfolded Protein ◽  
Cell Destruction ◽  
The Unfolded Protein Response ◽  
And Function

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.

scholarly journals The Endoplasmic Reticulum and Calcium Homeostasis in Pancreatic Beta Cells

Endocrinology ◽  
2019 ◽  
Vol 161 (2) ◽  
Author(s):  
Irina X Zhang ◽  
Malini Raghavan ◽  
Leslie S Satin
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Er Stress ◽  
Beta Cells ◽  
Unfolded Protein ◽  
Protein Response

Abstract The endoplasmic reticulum (ER) mediates the first steps of protein assembly within the secretory pathway and is the site where protein folding and quality control are initiated. The storage and release of Ca2+ are critical physiological functions of the ER. Disrupted ER homeostasis activates the unfolded protein response (UPR), a pathway which attempts to restore cellular equilibrium in the face of ER stress. Unremitting ER stress, and insufficient compensation for it results in beta-cell apoptosis, a process that has been linked to both type 1 diabetes (T1D) and type 2 diabetes (T2D). Both types are characterized by progressive beta-cell failure and a loss of beta-cell mass, although the underlying causes are different. The reduction of mass occurs secondary to apoptosis in the case of T2D, while beta cells undergo autoimmune destruction in T1D. In this review, we examine recent findings that link the UPR pathway and ER Ca2+ to beta cell dysfunction. We also discuss how UPR activation in beta cells favors cell survival versus apoptosis and death, and how ER protein chaperones are involved in regulating ER Ca2+ levels. Abbreviations: BiP, Binding immunoglobulin Protein ER; endoplasmic reticulum; ERAD, ER-associated protein degradation; IFN, interferon; IL, interleukin; JNK, c-Jun N-terminal kinase; KHE, proton-K+ exchanger; MODY, maturity-onset diabetes of young; PERK, PRKR-like ER kinase; SERCA, Sarco/Endoplasmic Reticulum Ca2+-ATPases; T1D, type 1 diabetes; T2D, type 2 diabetes; TNF, tumor necrosis factor; UPR, unfolded protein response; WRS, Wolcott–Rallison syndrome.

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 Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes

Endocrine ◽  
2015 ◽  
Vol 49 (3) ◽  
pp. 693-702 ◽  
Author(s):  
Ananta Poudel ◽  
Omid Savari ◽  
Deborah A. Striegel ◽  
Vipul Periwal ◽  
Jerome Taxy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Adult Onset ◽  
Onset Type ◽  
Beta Cell Destruction ◽  
Cell Destruction

scholarly journals Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study

Diabetes Care ◽  
2021 ◽  
Author(s):  
Susan Martin ◽  
Elena P. Sorokin ◽  
E. Louise Thomas ◽  
Naveed Sattar ◽  
Madeleine Cule ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Mendelian Randomization ◽  
Fat Content ◽  
Liver Fat ◽  
Liver And Pancreas ◽  
Pancreas Volume

OBJECTIVE Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations. RESEARCH DESIGN AND METHODS We used genetic variants associated (P < 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 32,859). We obtained summary-level data for risk of type 1 (9,358 cases) and type 2 (55,005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects. RESULTS Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27% increased risk and 0.76 [0.62, 0.94] or 24% decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes. CONCLUSIONS Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

scholarly journals The role of glycemic self-control in diabetes management: based on the American Diabetes Association guidelines (2021)

2021 ◽  
pp. 286-292
Author(s):  
G. E. Runova
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
American Diabetes Association ◽  
Diabetes Management ◽  
Glucose Monitoring ◽  
Self Monitoring ◽  
Diabetes Technology

Glycemic control represents an integral part of diabetes mellitus (DM) therapy. It is not surprising that diabetes technology is evolving to not only create new routes of insulin administration, but also to improve the measurement of glycemia. A significant number of new glucose monitoring systems have been launched to the market over the past 10 years. Nevertheless, only 30% of patients with type 1 diabetes and very few patients with type 2 diabetes use continuous or flash glucose monitoring. The reason for this is not only the cost and technical difficulties of continuous glucose monitoring, but also its clinical appropriateness. There is indisputable evidence that patients who receive intensified insulin therapy, especially those with type 1 diabetes, need frequent self-monitoring / continuous glucose monitoring. As for patients with type 2 diabetes receiving basal insulin and / or other antihyperglycemic therapy, the data received seem to be contradictory and uncertain. However, most of the recommendations simmer down to the need for self-monitoring of blood glucose levels in patients with type 2 diabetes. The diabetes technology section of the American Diabetes Association guidelines 2021 goes into details about the role of self-monitoring of blood glucose in diabetes management, including the need for continuous patient education on the principles and rules of self-monitoring, interpretation and practical use of the results of self-monitoring, various standards of glucometers, factors affecting the accuracy of the results. 

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