ArticleEndocrinology2013
Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Blocking IL-6 trans-signaling mitigates benzalkonium chloride-induced inflammation, oxidative imbalance, ER stress, and barrier disruption in human corneal epithelial cells.Eye and vision (London, England) · 2026Article
- Evidence for a Cytokine-Sensitive Network of Iron-Associated Genes That Protects Pancreatic Islets Against Ferroptosis.Metabolites · 2026Article
- Single-cell and proteomic profiling unveil aberrant immune phenotypes in gestational diabetes following assisted reproductive technology.Communications biology · 2026Article
- Circulating cytokines as triggers of endothelial dysfunction and sex-specific interstitial cell response in fibrocalcific aortic valve disease.International journal of biological sciences · 2026Article
- Association between stress hyperglycemia ratio and all-cause mortality in critically ill patients with mitral valve disease.Scientific reports · 2025Article
- Untargeted metabolomics reveals3 Biotech · 2025Article
- Exploring Allostatic Load as an Objective Measure of Stress Among U.S. Women With and Without HIV: A Pilot Study.Journal of women's health (2002) · 2025Article
- Profile of serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-12, adiponectin, and vitamin DClinical and experimental hepatology · 2025Article
- An Attomolar-Level Optical Device for Monitoring Receptor-Analyte Interactions Without Functionalization Steps: A Case Study of Cytokine Detection.Sensors (Basel, Switzerland) · 2025Article
- Review
- In Vivo Biocompatibility ofJournal of functional biomaterials · 2024Article
- Tipping-point transition from transient to persistent inflammation in pancreatic islets.NPJ systems biology and applications · 2024Article
- Salivary Profile Analysis Based on Oral Cancer Risk Habits: An Observational Cross-Sectional Study.Biomedicines · 2024Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
- Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.Biophysical chemistry · 2024Review
- Article
- Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids.Current research in pharmacology and drug discovery · 2024Review
- Central regulation of stress-evoked peripheral immune responses.Nature reviews. Neuroscience · 2023Review
- Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Elevated levels of circulating proinflammatory cytokines are associated with obesity and increased risk of type 2 diabetes, but the mechanism is unknown. We tested whether proinflammatory cytokines IL-1B+IL-6 at low picogram per milliliter concentrations (consistent with serum levels) could directly trigger pancreatic islet dysfunction. Overnight exposure to IL-1B+IL-6 in islets isolated from normal mice and humans disrupted glucose-stimulated intracellular calcium responses; cytokine-induced effects were more severe among islets from prediabetic db/db mice that otherwise showed no signs of dysfunction. IL-1B+IL-6 exposure reduced endoplasmic reticulum (ER) calcium storage, activated ER stress responses (Nos2, Bip, Atf4, and Ddit3 [CHOP]), impaired glucose-stimulated insulin secretion, and increased cell death only in islets from prediabetic db/db mice. Furthermore, we found increased serum levels of IL-1B and IL-6 in diabetes-prone mice at an age before hyperglycemia was exhibited, suggesting that low-grade systemic inflammation develops early in the disease process. In addition, we implanted normal outbred and inbred mice with subcutaneous osmotic mini-pumps containing IL-1B+IL-6 to mimic the serum increases found in prediabetic db/db mice. Both IL-1B and IL-6 were elevated in serum from cytokine-pump mice, but glucose tolerance and blood glucose levels did not differ from controls. However, when compared with controls, isolated islets from cytokine-pump mice showed deficiencies in calcium handling and insulin secretion that were similar to observations with islets exposed to cytokines in vitro. These findings provide proof of principle that low-grade systemic inflammation is present early in the development of type 2 diabetes and can trigger ER stress-mediated islet dysfunction that can lead to islet failure.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.