ArticleBMJ open diabetes research & care2016
Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes.
Article in BMJ open diabetes research & care, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Association BetweenFrontiers in endocrinology · 2021Pooled it
- The Hippo terminal effector YAP boosts enterovirus replication in type 1 diabetes.Nature communications · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Article
- CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity.Frontiers in genetics · 2023Article
- Environmental Factors and the Risk of Developing Type 1 Diabetes-Old Disease and New Data.Biology · 2022Review
- Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?Annual review of medicine · 2022Review
- Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells.iScience · 2022Article
- The etiology and pathogenesis of type 1 diabetes - A personal, non-systematic review of possible causes, and interventions.Frontiers in endocrinology · 2022Review
- Environmental Triggering of Type 1 Diabetes Autoimmunity.Frontiers in endocrinology · 2022Review
- β-Cell autophagy in the pathogenesis of type 1 diabetes.American journal of physiology. Endocrinology and metabolism · 2021Review
- Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.Cell host & microbe · 2021Article
- A rare case of fulminant type 1 diabetes mellitus accompanied by both acute pancreatitis and myocarditis - case report.BMC endocrine disorders · 2020Article
- Genetic Susceptibility of the Host in Virus-Induced Diabetes.Microorganisms · 2020Review
- Innate Viral Sensor MDA5 and Coxsackievirus Interplay in Type 1 Diabetes Development.Microorganisms · 2020Review
- Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge.Microorganisms · 2020Article
- Prospective virome analyses in young children at increased genetic risk for type 1 diabetes.Nature medicine · 2019Article
- Human Endogenous Retroviruses and Type 1 Diabetes.Current diabetes reports · 2019Review
- Article
- Enterovirus infection and type 1 diabetes: unraveling the crime scene.Clinical and experimental immunology · 2019Review
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesOne of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression.
designImmunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells.
resultsAn increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR.
conclusionsCAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.
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