ArticleGene therapy2005
Adenoviral overexpression of interleukin-1 receptor antagonist protein increases beta-cell replication in rat pancreatic islets.
Article in Gene therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 52 citations in OpenAlex.
- A Model for Human Islet Transplantation to Immunodeficient Streptozotocin-Induced Diabetic Mice.Cell transplantation · 2018Article
- Purification of replicating pancreatic β-cells for gene expression studies.Scientific reports · 2017Article
- Connecting type 1 and type 2 diabetes through innate immunity.Cold Spring Harbor perspectives in medicine · 2012Review
- Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade: evidence of improved immune regulation.Diabetes · 2012Article
- Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass.Diabetes · 2011Article
- Co-encapsulation of bioengineered IGF-II-producing cells and pancreatic islets: effect on beta-cell survival.Gene therapy · 2011Article
- In vivo diabetogenic action of CD4+ T lymphocytes requires Fas expression and is independent of IL-1 and IL-18.European journal of immunology · 2011Article
- Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.PloS one · 2011Article
- Sulfuretin protects against cytokine-induced beta-cell damage and prevents streptozotocin-induced diabetes.Experimental & molecular medicine · 2010Article
- Nardostachys jatamansi extract protects against cytokine-induced beta-cell damage and streptozotocin-induced diabetes.World journal of gastroenterology · 2010Article
- Cytokines in the Progression of Pancreatic β-Cell Dysfunction.International journal of endocrinology · 2010Article
- IL-1beta receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis.Journal of cellular physiology · 2009Article
- Bipartite adenoviral vector encoding hHGF and hIL-1Ra for improved human islet transplantation.Pharmaceutical research · 2009Article
- Article
- Thrombosis and inflammation in intraportal islet transplantation: a review of pathophysiology and emerging therapeutics.Journal of diabetes science and technology · 2008Article
- Resolving the conundrum of islet transplantation by linking metabolic dysregulation, inflammation, and immune regulation.Endocrine reviews · 2008Review
- Article
- Bipartite vector encoding hVEGF and hIL-1Ra for ex vivo transduction into human islets.Molecular pharmaceuticsArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The naturally occurring inhibitor of interleukin-1 (IL-1) action, interleukin-1 receptor antagonist protein (IRAP), binds to the type 1 IL-1 receptor but does not initiate IL-1 signal transduction. In this study, we have determined the effects of IL-1beta and IRAP overexpression on adult beta-cell replication and viability. IL-1beta reduced dramatically beta-cell replication in adult rat islets both at 5.5 mM (control: 0.29+/-0.04%; IL-1beta: 0.02+/-0.02%, P<0.05) and 22.2 mM glucose (control: 0.84+/-0.2%; IL-1beta: 0.05+/-0.05%, P<0.05). This effect was completely prevented in islets overexpressing IRAP after adenoviral gene transfer at 5.5 mM (Ad-IL-1Ra+IL-1beta: 0.84+/-0.1%, P<0.05) and 22.2 mM glucose (Ad-IL-1Ra+IL-1beta: 1.22+/-0.2%, P<0.05). Moreover, overexpression of IRAP increased glucose-stimulated beta-cell replication in the absence of IL-1beta exposure (Ad-IL-1Ra: 1.59+/-0.5%, P<0.05). beta-Cell death (TUNEL technique) was increased in IL-1beta-exposed islets but not in Ad-IL-1Ra-infected islets (control: 0.82+/-0.2%; control+IL-1beta: 1.77+/-0.2; IRAP: 0.61+/-0.2%; IRAP+IL-1beta: 0.86+/-0.1%, P<0.05). Comparable results were obtained by flow cytometry. To determine the effect of IRAP overexpression on beta-cell replication in vivo, Ad-IL-1Ra-transduced islets were transplanted into streptozotocin diabetic rats. beta-Cell replication was significantly increased in IRAP-overexpressing islet grafts (0.98+/-0.3%, P<0.05) compared to normal pancreas (0.35+/-0.02%), but not in control islet grafts (0.50+/-0.1%). This study shows that in addition to the effects of IL-1beta on beta-cell viability, this cytokine exerts a deleterious action on beta-cell replication, which can be prevented by IRAP overexpression, and provides support for the potential use of IRAP as a therapeutic tool.
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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.