The role of inflammation in insulitis and β-cell loss in type 1 diabetes
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with a strong inflammatory component. The latest studies indicate that innate immunity and inflammatory mediators have a much broader role in T1DM than initially assumed. Inflammation might contribute to early induction and amplification of the immune assault against pancreatic beta cells and, at later stages, to the stabilization and maintenance of insulitis. Inflammatory mediators probably contribute to the suppression of beta-cell function and subsequent apoptosis; they may also inhibit or stimulate beta-cell regeneration and might cause peripheral insulin resistance. The different effects of inflammation take place in different phases of the course of T1DM, and should be considered in the context of a 'dialog' between invading immune cells and the target beta cells. This dialog is mediated both by cytokines and chemokines that are released by beta cells and immune cells, and by putative, immunogenic signals that are delivered by dying beta cells. In this Review, we divided the role of inflammation in T1DM into three arbitrary stages: induction, amplification and maintenance or resolution of insulitis. These stages, and their progression or resolution, might depend on a patient's genetic background, which contributes to disease heterogeneity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [58]
Cites
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · see citing works
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932 · see citing works
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works
Interferons induce an antiviral state in human pancreatic islet cells
Hultcrantz, M., Hühn, M. H., Wolf, M., Olsson, A., Jacobson, S., Williams, B. R., Korsgren, O., & Flodström-Tullberg, M. (2007) · Virology · doi:10.1016/j.virol.2007.05.010 · Cited by 98 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407 · see citing works
Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878 · see citing works
Viral infections in type 1 diabetes mellitus — why the β cells?
Op de Beeck, A., & Eizirik, D. L. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.30 · Cited by 291 · see citing works
Self-citationA trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., et al. (2010) · Nature · doi:10.1038/nature09386 · Cited by 283 · see citing works
100 years of insulin: celebrating the past, present and future of diabetes therapy
Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A., & Evans-Molina, C. (2021) · Nature Medicine · doi:10.1038/s41591-021-01418-2 · Cited by 270 · see citing works
Early prediction of autoimmune (type 1) diabetes.
Regnell, S. E., & Lernmark, Å. (2017) · Diabetologia · doi:10.1007/s00125-017-4308-1 · Cited by 195 · see citing works
Insulitis in human type 1 diabetes: The quest for an elusive lesion
In't Veld, P. (2011) · Islets · doi:10.4161/isl.3.4.15728 · Cited by 216 · see citing works
Connexins: Key Mediators of Endocrine Function
Bosco, D., Haefliger, J.-A., & Meda, P. (2011) · Physiological Reviews · doi:10.1152/physrev.00027.2010 · Cited by 169 · see citing works
Approaching the in vitro clinical trial: engineering organs on chips
Capulli, A. K., Tian, K., Mehandru, N., Bukhta, A., Choudhury, S. F., Suchyta, M., & Parker, K. K. (2014) · Lab on a Chip · doi:10.1039/c4lc00276h · Cited by 111 · see citing works
Recent Lessons Learned From Prevention and Recent-Onset Type 1 Diabetes Immunotherapy Trials
Staeva, T. P., Chatenoud, L., Insel, R., & Atkinson, M. A. (2013) · Diabetes · doi:10.2337/db12-0562 · Cited by 91 · see citing works
Type I interferons and endoplasmic reticulum stress in health and disease
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.10.004 · Cited by 83 · see citing works
Dula, S. B., Jecmenica, M., Wu, R., Jahanshahi, P., Verrilli, G. M., Carter, J. D., Brayman, K. L., & Nunemaker, C. S. (2010) · Cell Calcium · doi:10.1016/j.ceca.2010.07.007 · Cited by 83 · see citing works
Pattern recognition receptor‐mediated inflammation in diabetic vascular complications
Wang, X., Antony, V., Wang, Y., Wu, G., & Liang, G. (2020) · Medicinal Research Reviews · doi:10.1002/med.21711 · Cited by 73 · see citing works
mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress
Chau, G. C., Im, D. U., Kang, T. M., Bae, J. M., Kim, W., Pyo, S., Moon, E.-Y., & Um, S. H. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201701085 · Cited by 67 · see citing works
Breaking Boundaries: Chronic Diseases and the Frontiers of Immune Microenvironments
Li, G., Wan, Y., Jiao, A., Jiang, K., Cui, G., Tang, J., Yu, S., Hu, Z., Zhao, S., Yi, Z., et al. (2025) · Med Research · doi:10.1002/mdr2.70007 · Cited by 63 · see citing works
Pugazhenthi, U., Velmurugan, K., Tran, A., Mahaffey, G., & Pugazhenthi, S. (2010) · Diabetologia · doi:10.1007/s00125-010-1849-y · Cited by 61 · see citing works
Genetic manipulation of stress pathways can protect stem-cell-derived islets from apoptosis in vitro
Leite, N. C., Pelayo, G. C., & Melton, D. A. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.01.018 · Cited by 36 · see citing works
Effects of oleanolic acid on inflammation and metabolism in diabetic rats
Iskender, H., Dokumacioglu, E., Terim Kapakin, K. A., Yenice, G., Mohtare, B., Bolat, I., & Hayirli, A. (2022) · Biotechnic & Histochemistry · doi:10.1080/10520295.2021.1954691 · Cited by 32 · see citing works
- Authors
- Eizirik, D. L., Colli, M. L., & Ortis, F.
- Affiliations
- Université Libre de Bruxelles (BE)
- ORCID
- Ortis, Fernanda
- Venue
- Nature Reviews Endocrinology
- Published
- 2009-04
- Volume
- 5
- Issue
- 4
- Pages
- 219-226
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2089934054
- Cited by
- 1,011
- References
- 4
- Citations by year
- 2026: 43 · 2025: 40 · 2024: 58 · 2023: 58 · 2022: 67 · 2021: 72 · 2020: 64 · 2019: 53 · 2018: 59 · 2017: 54 · 2016: 52 · 2015: 69 · 2014: 67 · 2013: 70 · 2012: 63
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, insulitis, beta cell destruction, inflammation, innate immunity, inflammatory mediators, beta-cell apoptosis, beta cell regeneration, insulin resistance, cytokines, chemokines, disease heterogeneity, autoimmune disease
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Inflammation, Islets of Langerhans, Insulin-Secreting Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
