ArticleMolecular metabolism2017
Amyloid formation disrupts the balance between interleukin-1β and interleukin-1 receptor antagonist in human islets.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Membrane Vesicles ofMicroorganisms · 2025Article
- Energy-Adjusted Dietary Inflammatory Index and Diabetes Risk in Postmenopausal Hispanic Women.Journal of the Academy of Nutrition and Dietetics · 2024Observational
- The trigger for pancreatic disease: NLRP3 inflammasome.Cell death discovery · 2023Review
- Advancements in innate immune regulation strategies in islet transplantation.Frontiers in immunology · 2023Review
- Role of signal transduction pathways in IL-1β-induced apoptosis: Pathological and therapeutic aspects.Immunity, inflammation and disease · 2023Review
- Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus.Frontiers in endocrinology · 2022Review
- Review
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- Proinflammatory Cytokine Interleukin 1β Disrupts β-cell Circadian Clock Function and Regulation of Insulin Secretion.Endocrinology · 2021Article
- Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021Article
- Low concentration IL-1β promotes islet amyloid formation by increasing hIAPP release from humanised mouse islets in vitro.Diabetologia · 2020Article
- Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death.Scientific reports · 2020Article
- Immune regulation of islet homeostasis and adaptation.Journal of molecular cell biology · 2020Review
- Alpha1-antitrypsin ameliorates islet amyloid-induced glucose intolerance and β-cell dysfunction.Molecular metabolism · 2020Article
- Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation.EBioMedicine · 2020Article
- Targeting the IL-1β/IL-1Ra pathways for the aggregation of human islet amyloid polypeptide in an ex vivo organ culture system of the intervertebral disc.Experimental & molecular medicine · 2019Article
- Inflammation in the Pathophysiology and Therapy of Cardiometabolic Disease.Endocrine reviews · 2019Review
- Islet inflammation in type 2 diabetes.Seminars in immunopathology · 2019Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
objectivesβ-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and β-cell death in T2D. We recently showed the role of interleukin-1β (IL-1β)/Fas/caspase-8 apoptotic pathway in amyloid-induced β-cell death. In this study, we used human islets in culture as an
methodsIsolated human islets (n = 10 donors) were cultured in elevated glucose (to form amyloid) with or without a neutralizing human IL-1β antibody for up to 7 days. Parallel studies were performed with human islets in which amyloid formation was prevented by adeno-siRNA-mediated suppression of hIAPP expression (as control). β-cell levels of IL-1Ra, Fas, apoptosis as well as islet function, insulin- and amyloid-positive areas, and IL-1Ra release were assessed.
resultsProgressive amyloid formation in human islets during culture was associated with alterations in IL-1Ra. Islet IL-1Ra levels were higher at early stages but were markedly reduced at later stages of amyloid formation. Furthermore, IL-1Ra release from human islets was reduced during 7-day culture in a time-dependent manner. These changes in IL-1Ra production and release from human islets during amyloid formation adversely correlated with islet IL-1β levels, β-cell Fas expression and apoptosis. Treatment with IL-1β neutralizing antibody markedly reduced amyloid-induced β-cell Fas expression and apoptosis, thereby improving islet β-cell survival and function during culture.
conclusionsThese data suggest that amyloid formation impairs the balance between IL-1β and IL-1Ra in islets by increasing IL-1β production and reducing IL-1Ra levels thereby promoting β-cell dysfunction and death. Restoring the IL-1β/IL-1Ra ratio may provide an effective strategy to protect islet β-cells from amyloid toxicity in T2D.
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