Immunobiology of β-Cell Destruction

ArticleinAdvances in Experimental Medicine and Biology 771:194-218 · January 2012with10 Reads
DOI: 10.1007/978-1-4614-5441-0_16 · Source: PubMed
Abstract
Type 1 diabetes is a chronic disease characterized by severe insulin deficiency and hyperglycemia, due to autoimmune destruction of pancreatic islets of Langerhans. A susceptible genetic background is necessary, but not sufficient, for the development of the disease. Epidemiological and clinical observations underscore the importance of environmental factors as triggers of type 1 diabetes, currently under investigation. Islet-specific autoantibodies precede clinical onset by months to years and are established tools for risk prediction, yet minor players in the pathogenesis of the disease. Many efforts have been made to elucidate disease-relevant defects in the key immune effectors of islet destruction, from the early failure of specific tolerance to the vicious circle of destructive insulitis. However, the events triggering islet autoimmunity as well as the transition to overt diabetes are still largely unknown, making prevention and treatment strategies still a challenge.
    • "These studies suggest that while not perfect, b-cell lines can serve as reasonable surrogate systems for studies of biochemical features of primary pancreatic b-cells. A thorough discussion of metabolomics applied to diabetes in general [7,8] or of all current mechanistic models of islet function [9] and dysfunction [2,10] is beyond the scope of this review, and we therefore refer the reader to excellent work elsewhere. Instead, we choose to focus the current review on new insights in islet biology derived from application of static and dynamic metabolic profiling methods, and the implications of this new information for translational applications. "
    [Show abstract] [Hide abstract] ABSTRACT: Metabolomics, the characterization of the set of small molecules in a biological system, is advancing research in multiple areas of islet biology. Measuring a breadth of metabolites simultaneously provides a broad perspective on metabolic changes as the islets respond dynamically to glucose or environmental stressors. As a result, metabolomics has the potential to provide new mechanistic insights into islet physiology and pathophysiology. Here we summarize advances in our understanding of islet physiology and the etiologies of type-1 and type-2 diabetes derived from metabolomics studies. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jun 2015
    • "T1D is one of the most common autoimmune disorders, characterized by a T cell-mediated destruction of insulinproducing beta cells in the pancreas. This condition is believed to result from the interaction between multiple genetic and environmental factors, many of which are still poorly understood [13]. Former studies have shown that auto-antibodies against ZnT8 are common in newly-diagnosed cases of T1D [5], thus suggesting that this beta-cell membrane protein may act as a major autoantigen in T1D [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: PURPOSE: MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. METHODS: Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. RESULTS: Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference (P = 0.016). CONCLUSIONS: This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions. PMID: 25226393 [PubMed - as supplied by publisher]
    Full-text · Article · Sep 2014
    • "T1D is one of the most common autoimmune disorders, characterized by a T cell-mediated destruction of insulinproducing beta cells in the pancreas. This condition is believed to result from the interaction between multiple genetic and environmental factors, many of which are still poorly understood [13]. Former studies have shown that auto-antibodies against ZnT8 are common in newly-diagnosed cases of T1D [5], thus suggesting that this beta-cell membrane protein may act as a major autoantigen in T1D [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference (P = 0.016). Conclusions This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.
    Full-text · Article · Sep 2014
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