Viral infections as potential triggers of type 1 diabetes

Werf, Nienke van der; Kroese, Frans G. M.; Rozing, Jan; Hillebrands, Jan-Luuk

doi:10.1002/dmrr.695

Cited by 194 publications

(149 citation statements)

References 151 publications

(202 reference statements)

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“…Dietary antigens inclusive of wheat gluten may thus have an important role in modulating diabetes onset. Additionally, viral infections are associated with the onset of type 1 diabetes (particularly enteroviruses and rotaviruses) and also affect gut permeability [33,34]. Reports have shown that children with type 1 diabetes have increased barrier defects in their small intestines ( [8] and reviewed in [35]) and have a higher incidence of enteroviral infections [36].…”

Section: Discussionmentioning

confidence: 99%

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

et al. 2009

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Aims/hypothesis Increased exposure to enteric microbes as a result of intestinal barrier disruption is thought to contribute to the development of several intestinal inflammatory diseases; however, it less clear whether such exposure modulates the development of extra-intestinal inflammatory and autoimmune diseases. The goal of this study was to examine the potential role of pathogenic enteric microbes and intestinal barrier dysfunction in the pathogenesis of type 1 diabetes. Methods Using NOD mice, we assessed: (1) intrinsic barrier function in mice at different ages by measuring serum levels of FITC-labelled dextran; and (2) the impact on insulitis development of infection by strains of an enteric bacterial pathogen (Citrobacter rodentium) either capable (wild-type) or incapable (lacking Escherichia coli secreted protein F virulence factor owing to deletion of the gene [ΔespF]) of causing intestinal epithelial barrier disruption. Results Here we demonstrate that prediabetic (12-weekold) NOD mice display increased intestinal permeability compared with non-obese diabetes-resistant and C57BL/6 mice. We also found that young (4-week-old) NOD mice infected with wild-type C. rodentium exhibited accelerated development of insulitis in concert with infection-induced barrier disruption. In contrast, insulitis development was not altered in NOD mice infected with the non-barrier-disrupting ΔespF strain. Moreover, C. rodentium-infected NOD mice demonstrated increased activation and proliferation of pancreatic-draining lymph node T cells, including diabetogenic CD8 + T cells, compared with uninfected NOD mice. Conclusions/interpretation This is the first demonstration that a loss of intestinal barrier integrity caused by an enteric bacterial pathogen results in the activation of diabetogenic CD8 + T cells and modulates insulitis.

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Section: Discussionmentioning

confidence: 99%

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

et al. 2009

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“…cow milk), vaccination, toxins and the physiological betacell turnover occurring in the newborn (11,12). Accumulating evidence points to viral infections by enterovirus, rubella, mumps, rotavirus, parvovirus or cytomegalovirus as the most probable candidates for triggering beta-cell autoimmunity (13). Particular attention is given to the enteroviruses which have a specific tropism for the pancreas (13).…”

Section: Onset Of T1d: Environmental Triggers Recruitment and Activamentioning

confidence: 99%

“…Accumulating evidence points to viral infections by enterovirus, rubella, mumps, rotavirus, parvovirus or cytomegalovirus as the most probable candidates for triggering beta-cell autoimmunity (13). Particular attention is given to the enteroviruses which have a specific tropism for the pancreas (13). Epidemiological studies investigating the seasonal appearance of betacell autoantibodies in a group of risk individuals showed preferential emergence of the self-antibodies during the cold season, correlating with a period of increased enterovirus infections (11).…”

Section: Onset Of T1d: Environmental Triggers Recruitment and Activamentioning

confidence: 99%

Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes

Pirot

Cardozo

Eizirik

2008

Arq Bras Endocrinol Metab

136

113

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type 1 diabetes mellitus (t1d) is characterized by severe insulin deficiency resulting from chronic and progressive destruction of pancreatic beta-cells by the immune system. the triggering of autoimmunity against the beta-cells is probably caused by environmental agent(s) acting in the context of a predisposing genetic background. once activated, the immune cells invade the islets and mediate their deleterious effects on beta-cells via mechanisms such as Fas/Fasl, perforin/granzyme, reactive oxygen and nitrogen species and pro-inflammatory cytokines. Binding of cytokines to their receptors on the beta-cells activates MAP-kinases and the transcription factors stAt-1 and nFκ-B, provoking functional impairment, endoplasmic reticulum stress and ultimately apoptosis. this review discusses the potential mediators and mechanisms leading to beta-cell destruction in t1d. Keywords: Pancreatic beta-cell; diabetes mellitus; Apoptosis; cytokines; endoplasmic reticulum; er stress RESuMOMecanismos de Destruição e Morte da Célula-beta Pancreática no Diabetes. o diabetes melito tipo 1 (dM1) tem como característica uma grave deficiência de insulina que resulta da destruição da célula-beta, crônica e progressiva, pelo sistema imune. o desencadeamento da autoimunidade contra a célula-beta é causado, provavelmente, por agentes ambientais que atuam quando existe predisposição genética. uma vez ativadas, células imunes invadem as ilhotas, e os efeitos deletérios sobre as células-beta são mediados por mecanismos relacionados a Fas/Fasl, perforina/granzima, espécies reativas de oxigênio e nitrogênio, e a citocinas pró-inflamatórias. A ligação de citocinas a seus receptores na célula-beta ativa MAP-quinase e fatores de transcrição stAt-1 e nFkB, provocando prejuízo funcional, estresse de retículo endoplasmático e, por fim, apoptose. esta revisão discute os mecanismos e os mediadores potenciais que levam à destruição da célula-beta no dM1. Descritores: célula-beta pancreática; diabetes melito; Apoptose; citocinas; estresse do retículo endoplasmático thE GENEtic BAcKGROuND Of typE 1 DiABEtES MEllituS (t1D)

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“…This process, which occurs in genetically susceptible individuals, is triggered by environmental factors [2]. The underlying, mediating environmental factors are not known, although several factors have been proposed, including viral infections [3], dietary factors such as cow's milk protein and gluten [4], environmental toxins [5], increased weight gain in infancy [6] and antenatal factors such as maternal age [7] and birth order [8]. Data on the aetiology of type 1 diabetes are largely based on studies of type 1 diabetes cases diagnosed in children younger than 15 years.…”

Section: Introductionmentioning

confidence: 99%

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults

Lammi

Moltchanova²,

Blomstedt³

et al. 2007

Diabetologia

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Aims/hypothesis The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. Methods Data on all cases of type 1 diabetes (n=1,345) and type 2 diabetes (n=1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. Results There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. Conclusions/interpretation Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.

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Viral infections as potential triggers of type 1 diabetes

Cited by 194 publications

References 151 publications

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice

Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults

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