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  1. Article ; Online: Autoimmune vulnerability of beta versus alpha cells might be due to increased 2',5' synthetase.

    Buschard, Karsten / Haupt-Jorgensen, Martin

    APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

    2024  Volume 132, Issue 5, Page(s) 371–372

    MeSH term(s) Humans ; Interferons
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2024-02-12
    Publishing country Denmark
    Document type Letter
    ZDB-ID 93340-5
    ISSN 1600-0463 ; 0903-4641
    ISSN (online) 1600-0463
    ISSN 0903-4641
    DOI 10.1111/apm.13384
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    Ud II Zs.73: Show issues Location:
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  2. Article ; Online: Failure to replicate the diabetes alleviating effect of a maternal gluten-free diet in non-obese diabetic mice.

    Mønsted, Mia Øgaard / Holm, Laurits Juulskov / Buschard, Karsten / Haupt-Jorgensen, Martin

    PloS one

    2023  Volume 18, Issue 9, Page(s) e0289258

    Abstract: Type 1 diabetes (T1D) is an autoimmune disease with an unexplained rising incidence for which environmental factors like gluten may play a role. Previously, we showed that a gluten-free (GF) diet provided strictly in utero reduces the autoimmune diabetes ...

    Abstract Type 1 diabetes (T1D) is an autoimmune disease with an unexplained rising incidence for which environmental factors like gluten may play a role. Previously, we showed that a gluten-free (GF) diet provided strictly in utero reduces the autoimmune diabetes incidence in Non-Obese Diabetic (NOD) mice compared to a gluten-containing standard (STD) diet. The current study was initiated to elucidate possible mechanisms behind the diabetes-alleviating effect of the same diet intervention. NOD mice received either a GF Altromin diet or a STD Altromin diet during pregnancy. Female offspring from both groups were fed a STD diet throughout life and their diabetes incidence was recorded for 200 days. The following parameters were measured in 13-week-old female offspring: insulitis degree, glucose and insulin tolerance, and plasma insulin autoantibody titer. The diet intervention showed no reduction in autoimmune diabetes incidence, insulitis degree, glucose nor insulin tolerance and plasma insulin autoantibody titer. In conclusion, this study could not replicate the previously observed diabetes alleviative effects of a maternal gluten-free diet in NOD mouse offspring and could therefore not further elucidate potential mechanisms.
    MeSH term(s) Animals ; Female ; Mice ; Pregnancy ; Autoantibodies ; Diabetes Mellitus, Experimental/diet therapy ; Diabetes Mellitus, Type 1/diet therapy ; Diet, Gluten-Free ; Glucose ; Glutens ; Insulins ; Mice, Inbred NOD ; Maternal Nutritional Physiological Phenomena
    Chemical Substances Autoantibodies ; Glucose (IY9XDZ35W2) ; Glutens (8002-80-0) ; Insulins
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0289258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Editorial: The gut-pancreas axis in type 1 diabetes - a focus on environmental factors.

    Fløyel, Tina / Funda, David / Dodero, Veronica I / Haupt-Jorgensen, Martin

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1270297

    MeSH term(s) Humans ; Diabetes Mellitus, Type 1 ; Pancreas ; Abdomen
    Language English
    Publishing date 2023-08-15
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1270297
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  4. Article ; Online: Can a gluten-free diet be partly protective for COVID-19 infection?

    Haupt-Jorgensen, Martin / Buschard, Karsten

    APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

    2020  Volume 128, Issue 10, Page(s) 558–559

    MeSH term(s) Alveolar Epithelial Cells/drug effects ; Alveolar Epithelial Cells/metabolism ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus/drug effects ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/diagnosis ; Coronavirus Infections/diet therapy ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Databases, Factual ; Diet, Gluten-Free ; Enterocytes/drug effects ; Enterocytes/metabolism ; Gene Expression Regulation/drug effects ; Glutens/administration & dosage ; Host-Pathogen Interactions/drug effects ; Humans ; Nicotine/administration & dosage ; Pandemics/prevention & control ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/diet therapy ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Severity of Illness Index ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Tobacco Smoking/metabolism
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Nicotine (6M3C89ZY6R) ; Glutens (8002-80-0) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-08-27
    Publishing country Denmark
    Document type Letter
    ZDB-ID 93340-5
    ISSN 1600-0463 ; 0903-4641
    ISSN (online) 1600-0463
    ISSN 0903-4641
    DOI 10.1111/apm.13075
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    Ud II Zs.73: Show issues Location:
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  5. Article ; Online: Elevated cathepsin S serum levels in new-onset type 1 diabetes and autoantibody-positive siblings.

    Frørup, Caroline / Jensen, Mathias Høj / Haupt-Jorgensen, Martin / Buschard, Karsten / Størling, Joachim / Pociot, Flemming / Fløyel, Tina

    Diabetes

    2024  

    Abstract: Accumulating data suggest a role for the lysosomal protease cathepsin S (CTSS) in type 1 diabetes. Circulating CTSS is increased in type 1 diabetes; however, whether CTSS has protective or deleterious effects is unclear. The study's objectives were to ... ...

    Abstract Accumulating data suggest a role for the lysosomal protease cathepsin S (CTSS) in type 1 diabetes. Circulating CTSS is increased in type 1 diabetes; however, whether CTSS has protective or deleterious effects is unclear. The study's objectives were to examine the biomarker potential of CTSS in new-onset type 1 diabetes, and to investigate the expression and secretion of CTSS in human islets and β cells. The CTSS level was analyzed in serum from children with new-onset type 1 diabetes and autoantibody-positive and -negative siblings by ELISA. The expression and secretion of CTSS were evaluated in isolated human islets and EndoC-βH5 cells by real-time qPCR, immunoblotting, and ELISA. The CTSS serum level was elevated in children with new-onset type 1 diabetes and positively associated with autoantibody status in healthy siblings. Human islets and EndoC-βH5 cells demonstrated induction and secretion of CTSS after exposure to pro-inflammatory cytokines, a model system of islet inflammation. Analysis of publicly available single-cell RNA sequencing data on human islets showed that elevated CTSS expression was exclusive for the β cells in donors with type 1 diabetes as compared to non-diabetic donors. These findings suggest a potential of CTSS as a diagnostic biomarker in type 1 diabetes.
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db23-0911
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  7. Article ; Online: Can a gluten‐free diet be partly protective for COVID‐19 infection?

    Haupt‐Jorgensen, Martin / Buschard, Karsten

    APMIS

    2020  Volume 128, Issue 10, Page(s) 558–559

    Keywords Immunology and Allergy ; Pathology and Forensic Medicine ; Microbiology (medical) ; General Medicine ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 913841-9
    ISSN 0903-4641
    ISSN 0903-4641
    DOI 10.1111/apm.13075
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Type 1 diabetes could begin with alterations in innate anti-viral immunity, which are already at this stage associated with HLA risk haplotypes.

    Buschard, Karsten / Jensen, Mathias Høj / Krogvold, Lars / Gerling, Ivan C / Dahl-Jørgensen, Knut / Pedersen, Kristina / Haupt-Jorgensen, Martin

    Diabetes/metabolism research and reviews

    2023  Volume 39, Issue 7, Page(s) e3678

    Abstract: Aims: To investigate if HLA risk haplotypes and HbA1c levels are associated with the expression levels of innate anti-viral immune pathway genes in type 1 diabetes.: Materials and methods: We investigated RNA expression levels of innate anti-viral ... ...

    Abstract Aims: To investigate if HLA risk haplotypes and HbA1c levels are associated with the expression levels of innate anti-viral immune pathway genes in type 1 diabetes.
    Materials and methods: We investigated RNA expression levels of innate anti-viral immune pathway genes in laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection study and the network of Pancreatic Organ Donors in relation to HLA risk haplotypes (non-predisposed and predisposed) and HbA1c levels (normal, elevated, and high).
    Results: The expression of innate anti-viral immune genes (TLR7, OAS1, OAS3 etc.) was significantly increased in individuals with predisposing vs non-predisposing HLA haplotypes. Also, the expression of several of the innate anti-viral immune genes from the HLA risk haplotype analysis was significantly increased in the group with high vs normal HbA1c. Furthermore, the gene expression of OAS2 was significantly increased in the group with high HbA1c vs elevated HbA1c.
    Conclusions: Expression of innate anti-viral immune pathway genes was increased in individuals with predisposing HLA risk haplotypes and those with high HbA1c. This indicates that type 1 diabetes might well begin with alterations in innate anti-viral immunity, and already at this stage be associated with HLA risk haplotypes.
    Language English
    Publishing date 2023-07-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 1470192-3
    ISSN 1520-7560 ; 1520-7552
    ISSN (online) 1520-7560
    ISSN 1520-7552
    DOI 10.1002/dmrr.3678
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    Zs.A 2119: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  9. Article ; Online: The anti-inflammatory agent 5-ASA reduces the level of specific tsRNAs in sperm cells of high-fat fed C57BL/6J mouse sires and improves glucose tolerance in female offspring.

    Bak, Stine Thorhauge / Haupt-Jorgensen, Martin / Dudele, Anete / Wegener, Gregers / Wang, Tobias / Nielsen, Anders Lade / Lund, Sten

    Journal of diabetes and its complications

    2023  Volume 37, Issue 9, Page(s) 108563

    Abstract: Introduction: The prevalence of obesity and associated comorbidities have increased to epidemic proportions globally. Paternal obesity is an independent risk factor for developing obesity and type 2 diabetes in the following generation, and growing ... ...

    Abstract Introduction: The prevalence of obesity and associated comorbidities have increased to epidemic proportions globally. Paternal obesity is an independent risk factor for developing obesity and type 2 diabetes in the following generation, and growing evidence suggests epigenetic inheritance as a mechanism for this predisposition. How and why obesity induces epigenetic changes in sperm cells remain to be clarified in detail. Yet, recent studies show that alterations in sperm content of transfer RNA-derived small RNAs (tsRNAs) can transmit the effects of paternal obesity to offspring. Obesity is closely associated with low-grade chronic inflammation. Thus, we evaluated whether the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) could intervene in the transmission of epigenetic inheritance of paternal obesity by reducing the inflammatory state in obese fathers.
    Methods: Male C57BL/6JBomTac mice were either fed a high-fat diet or a high-fat diet with 5-ASA for ten weeks before mating. The offspring metabolic phenotype was evaluated, and spermatozoa from sires were isolated for assessment of specific tsRNAs levels.
    Results: 5-ASA intervention reduced the levels of Glu-CTC tsRNAs in sperm cells and improved glucose tolerance in female offspring fed a chow diet. Paternal high-fat diet-induced obesity per se had only a moderate impact on the metabolic phenotype of both male and female offspring in our setting.
    Conclusion: The results indicate that the low-grade inflammatory response associated with obesity may be an important factor in epigenetic inheritance of paternal obesity.
    MeSH term(s) Mice ; Animals ; Male ; Female ; Diabetes Mellitus, Type 2/complications ; Mice, Inbred C57BL ; Semen/metabolism ; Obesity/complications ; Obesity/genetics ; Obesity/metabolism ; Spermatozoa ; Diet, High-Fat/adverse effects ; Anti-Inflammatory Agents ; Glucose/metabolism
    Chemical Substances Anti-Inflammatory Agents ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-07-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1105840-7
    ISSN 1873-460X ; 1056-8727
    ISSN (online) 1873-460X
    ISSN 1056-8727
    DOI 10.1016/j.jdiacomp.2023.108563
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    Zs.A 2225: Show issues Location:
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  10. Article: PPARs and the Development of Type 1 Diabetes.

    Holm, Laurits J / Mønsted, Mia Øgaard / Haupt-Jorgensen, Martin / Buschard, Karsten

    PPAR research

    2020  Volume 2020, Page(s) 6198628

    Abstract: Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate ... ...

    Abstract Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate insulin secretion and T cell differentiation, respectively. Moreover, various PPAR agonists prevent diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. PPARs are thus of interest in type 1 diabetes (T1D) as they represent a novel approach targeting both the pancreas and the immune system. In this review, we examine the role of PPARs in immune responses and beta cell biology and their potential as targets for treatment of T1D.
    Language English
    Publishing date 2020-01-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2237981-2
    ISSN 1687-4765 ; 1687-4757
    ISSN (online) 1687-4765
    ISSN 1687-4757
    DOI 10.1155/2020/6198628
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