ArticleDiabetologia2013
Production and function of IL-12 in islets and beta cells.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.Nature communications · 2024Article
- The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.Frontiers in endocrinology · 2024Review
- Prevention of Autoimmune Diabetes in NOD Mice by Dimethyl Fumarate.Antioxidants (Basel, Switzerland) · 2021Article
- Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health.Journal of developmental origins of health and disease · 2019Article
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
- Insights on the Role of Putative Muscle-Derived Factors on Pancreatic Beta Cell Function.Frontiers in physiology · 2019Review
- Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.Diabetes · 2017Article
- Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes.Clinical reviews in allergy & immunology · 2017Review
- Periodontitis aggravated pancreatic β-cell dysfunction in diabetic mice through interleukin-12 regulation on Klotho.Journal of diabetes investigation · 2016Article
- The analysis of correlation between IL-12 gene expression and hepatitis B virus in the affected patients.Virusdisease · 2015Article
- Expression pattern of 12-lipoxygenase in human islets with type 1 diabetes and type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2015Article
- Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction.Diabetologia · 2015Article
- Interleukin-12 (IL-12)/STAT4 Axis Is an Important Element for β-Cell Dysfunction Induced by Inflammatory Cytokines.PloS one · 2015Article
- New insight on human type 1 diabetes biology: nPOD and nPOD-transplantation.Current diabetes reports · 2014Review
- Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes.Diabetologia · 2014Article
- The Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors with Diabetes (nPOD) Program: goals, operational model and emerging findings.Pediatric diabetes · 2014Review
- Review
- Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease.Diabetes, obesity & metabolism · 2013Review
- Islet inflammation: a unifying target for diabetes treatment?Trends in endocrinology and metabolism: TEM · 2013Review
- Gastric inhibitory polypeptide receptor methylation in newly diagnosed, drug-naïve patients with type 2 diabetes: a case-control study.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisIL-12 is an important cytokine in early inflammatory responses and is implicated in the immune-mediated pathogenesis of pancreatic islets in diabetes. However, little is known about the direct effects of IL-12 on islets and beta cells.
methodsIn this study, beta cell function, gene expression and protein production were assessed in primary human donor islets and murine beta cell lines in response to stimulation with IL-12 or a pro-inflammatory cytokine cocktail (TNF-α, IL-1β and IFN-γ).
resultsThe pro-inflammatory cytokine cocktail induced islet dysfunction and potently increased the expression and production of IL-12 ligand and IL-12 receptor in human islets. In human islets, the receptor for IL-12 co-localised to the cell surface of insulin-producing cells. Both IL-12 ligand and IL-12 receptor are expressed in the homogeneous beta cell line INS-1. IL-12 induced changes in gene expression, including a dose-dependent upregulation of IFNγ (also known as IFNG), in INS-1 cells. A neutralising antibody to IL-12 directly inhibited IFNγ gene expression in human donor islets induced by either IL-12 or pro-inflammatory cytokine stimulation. Functionally, IL-12 impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cells and human donor islets. A neutralising antibody to IL-12 reversed the beta cell dysfunction (uncoupling of GSIS or induction of caspase-3 activity) induced by pro-inflammatory cytokines. CONCLUSIONS/
interpretationThese data identify beta cells as a local source of IL-12 ligand and suggest a direct role of IL-12 in mediating beta cell pathology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.