The role of inflammation in insulitis and β-cell loss in type 1 diabetes

2009 ◽  
Vol 5 (4) ◽  
pp. 219-226 ◽  
Author(s):  
Décio L. Eizirik ◽  
Maikel L. Colli ◽  
Fernanda Ortis
Keyword(s):  
Type 1 Diabetes ◽  
Cell Loss ◽  
Β Cell

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.

Harnessing immune cells to enhance β-cell mass in type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Ercument Dirice ◽  
Rohit N Kulkarni
Keyword(s):  
Type 1 Diabetes ◽  
Mononuclear Cells ◽  
Islet Cells ◽  
Cell Mass ◽  
Cell Loss ◽  
Cell Types ◽  
Β Cells ◽  
Β Cell ◽  
Autoimmune Attack

Type 1 diabetes is characterized by early β-cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the β cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing β cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including β cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote β-cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease.

scholarly journals IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes

JCI Insight ◽  
2021 ◽  
Vol 6 (21) ◽  
Author(s):  
Carla J. Greenbaum ◽  
Elisavet Serti ◽  
Katharina Lambert ◽  
Lia J. Weiner ◽  
Sai Kanaparthi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Loss ◽  
Receptor Blockade ◽  
Β Cell ◽  
Onset Type ◽  
New Onset

scholarly journals Circulating Differentially Methylated Amylin DNA as a Biomarker of β-Cell Loss in Type 1 Diabetes

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152662 ◽  
Author(s):  
John A. Olsen ◽  
Lauren A. Kenna ◽  
Michael G. Spelios ◽  
Martin J. Hessner ◽  
Eitan M. Akirav
Keyword(s):  
Type 1 Diabetes ◽  
Cell Loss ◽  
Β Cell

scholarly journals Type 1 diabetes mellitus: most recent advances in its pathogenesis and treatment

2012 ◽  
Vol 153 (27) ◽  
pp. 1047-1056 ◽  
Author(s):  
András Zóka ◽  
Anikó Somogyi ◽  
Gábor Firneisz
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Protective Role ◽  
Therapeutic Approaches ◽  
Β Cell ◽  
Mhc Genes ◽  
Prevalence Of Diabetes Mellitus

The incidence and prevalence of diabetes mellitus is globally increasing. The causes of this trend are relatively obvious in the case of type 2 diabetes. In contrast, in case of type 1 diabetes the amount of available data is continuously growing, but the causes are not so well defined. The genetic risk, especially related to the MHC genes is well known, and the increasing amount of data underlines the role of additional risks due to non-MHC genetic polimorphisms. Hopefully, they will provide the basis for future diagnostic and therapeutic approaches. There is increasing knowledge about the pathophysiological aspects including the role of immunological disregulation (balance of autotolerance, role of regulatory T-cells) and environmental triggers (nutrients, viruses). Information on the entero-insular axis and the β-cell protective role of incretin hormones might offer an opportunity for new therapeutic strategies. In this paper, the authors try to summarize some current aspects of the pathomechanism and related therapeutic approaches. Orv. Hetil., 2012, 153, 1047–1056.

scholarly journals BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

2015 ◽  
Vol 172 (2) ◽  
pp. 107-113 ◽  
Author(s):  
A Lauria ◽  
A Barker ◽  
N Schloot ◽  
N Hosszufalusi ◽  
J Ludvigsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Body Weight ◽  
Cell Function ◽  
Independent Predictor ◽  
Insulin Dose ◽  
Cell Loss ◽  
Β Cell ◽  
C Peptide ◽  
Β Cell Function

ObjectiveBody weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis.DesignMulticentre longitudinal study carried out at diagnosis and up to 1-year follow-up.MethodsData on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (<5 years, n=126; >5 years <10 years, n=295; >10 years <18 years, n=421; >18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c.ResultsIn individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10–18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (β 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m2 higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (β=0.026, 95% CI=0.0097, 0.042; P=0.002).ConclusionsThese observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10–18 years. This should be considered in studies of β-cell function in type 1 diabetes.

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