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Cited by 104Diabetes and associated disordersPancreatic function and diabetesGenetic Associations and Epidemiology

CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

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Fløyel, Tina, Brorsson, Caroline, Nielsen, Lotte B., Miani, Michela, Bang-Berthelsen, Claus Heiner, Friedrichsen, Martin, Overgaard, Anne Julie, Berchtold, Lukas A. +19 more·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1402571111PMC PMC4104872
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Abstract

Significance: In type 1 diabetes (T1D), the insulin-producing pancreatic β-cells are destroyed by the immune system. Both genetic and environmental factors contribute to T1D risk. Candidate genes for T1D identified by genome-wide association studies have been proposed to act at both the immune system and the β-cell levels. This study shows that the risk variant rs3825932 in the candidate gene cathepsin H ( CTSH ) predicts β-cell function in both model systems and human T1D. Collectively, our data indicate that higher CTSH expression in β-cells may protect against immune-mediated damage and preserve β-cell function, thereby representing a possible therapeutic target. Our study reinforces the concept that candidate genes for T1D may affect disease progression by modulating survival and function of the β-cells.

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  • Over 40% of genes associated with type 1 diabetes are expressed in the islet or beta cell.

    “More recently, there has been increased focus on whether many of these variants may influence beta cell interactions with the immune system, with over 40% of genes associated with type 1 diabetes being expressed in the islet or beta cell.”

    From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [56]

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Research works printed but not linked: 31

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Authors
Fløyel, T., Brorsson, C., Nielsen, L. B., Miani, M., Bang-Berthelsen, C. H., Friedrichsen, M., Overgaard, A. J., Berchtold, L. A., Wiberg, A., Poulsen, P., Hansen, L., Rosinger, S., Boehm, B. O., Ram, R., Nguyen, Q., Mehta, M., Morahan, G., Concannon, P., Bergholdt, R., Nielsen, J. H., Reinheckel, T., von Herrath, M., Vaag, A., Eizirik, D. L., Mortensen, H. B., Størling, J., & Pociot, F.
Affiliations
  • Herlev Hospital (DK)
  • Université Libre de Bruxelles (BE)
  • Department of Pediatrics, Herlev University Hospital, 2730 Herlev, Denmark;
  • Rigshospitalet (DK)
  • La Jolla Institute for Immunology (US)
  • Novo Nordisk (Denmark) (DK)
  • Universität Ulm (DE)
  • Nanyang Technological University (SG)
  • The University of Western Australia (AU)
  • University of Florida (US)
  • University of Copenhagen (DK)
  • University of Freiburg (DE)
  • Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2014-06-30
Volume
111
Issue
28
Pages
10305-10310
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1402571111
PMC
PMC4104872
OpenAlex
W2146237406
Cited by
104
References
3
Citations by year
2026: 2 · 2025: 16 · 2024: 13 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 9 · 2015: 13 · 2014: 1
FWCI
6.35
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK085678, R01DK046635)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
cathepsin H, type 1 diabetes, disease progression, beta-cell function, beta-cell apoptosis, inflammatory cytokines, JNK signaling, p38 MAPK, building information modeling, c-Myc, Ins2, insulin secretion, genetic susceptibility, newly diagnosed type 1 diabetes, glucose tolerance
MeSH terms
Adolescent, Alleles, Animals, Cell Line, Child, Child, Preschool, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Gene Expression Regulation, Genotype, Humans, Apoptosis, Mice, Knockout, Insulin-Secreting Cells, Mice, Rats, Cathepsin H

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