ArticlePloS one2012
Analysis of beta-cell gene expression reveals inflammatory signaling and evidence of dedifferentiation following human islet isolation and culture.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 132 citations in OpenAlex.
- ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation.Cell stem cell · 2025Article
- Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p.Scientific reports · 2025Article
- Perlecan: An Islet Basement Membrane Protein with Protective Anti-Inflammatory Characteristics.Bioengineering (Basel, Switzerland) · 2024Article
- Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum.Science advances · 2024Article
- Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver.Advanced healthcare materials · 2024Article
- Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis.PLoS computational biology · 2024Article
- Pancreatic β-Cell Identity Change through the Lens of Single-Cell Omics Research.International journal of molecular sciences · 2024Review
- Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy.EMBO molecular medicine · 2023Article
- The inhibition of FKBP5 protects β-cell survival under inflammation stress via AKT/FOXO1 signaling.Cell death discovery · 2023Article
- Insulin secretion hot spots in pancreatic β cells as secreting adhesions.Frontiers in cell and developmental biology · 2023Article
- Every islet matters: improving the impact of human islet research.Nature metabolism · 2022Review
- Similarities in Calcium Oscillations Between Neonatal Mouse Islets and Mature Islets Exposed to Chronic Hyperglycemia.Endocrinology · 2022Article
- Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.Molecular & cellular proteomics : MCP · 2022Article
- The Influence of Microenvironment on Survival of Intraportal Transplanted Islets.Frontiers in immunology · 2022Review
- Article
- The Foundation for Engineering a Pancreatic Islet Niche.Frontiers in endocrinology · 2022Review
- An accomplice more than a mere victim: The impact of β-cell ER stress on type 1 diabetes pathogenesis.Molecular metabolism · 2021Review
- Targeting β-cell dedifferentiation and transdifferentiation: opportunities and challenges.Endocrine connections · 2021Review
- Review
- A Systematic Comparison of Protocols for Recovery of High-Quality RNA from Human Islets Extracted by Laser Capture Microdissection.Biomolecules · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stresses encountered during islet isolation and culture may have deleterious effects on beta-cell physiology. However, the biological response of human islet cells to isolation remains poorly characterized. A better understanding of the network of signaling pathways induced by islet isolation and culturing may lead to strategies aimed at improving islet graft survival and function. Laser capture microdissection (LCM) was used to extract beta-cell RNA from 1) intact pancreatic islets, 2) freshly isolated islets, 3) islets cultured for 3 days, and changes in gene expression were examined by microarray analysis. We identified a strong inflammatory response induced by islet isolation that continues during in-vitro culture manifested by upregulation of several cytokines and cytokine-receptors. The most highly upregulated gene, interleukin-8 (IL-8), was induced by 3.6-fold following islet isolation and 56-fold after 3 days in culture. Immunofluorescence studies showed that the majority of IL-8 was produced by beta-cells themselves. We also observed that several pancreas-specific transcription factors were down-regulated in cultured islets. Concordantly, several pancreatic progenitor cell-specific transcription factors like SOX4, SOX9, and ID2 were upregulated in cultured islets, suggesting progressive transformation of mature beta-cell phenotype toward an immature endocrine cell phenotype. Our findings suggest islet isolation and culture induces an inflammatory response and loss of the mature endocrine cell phenotype. A better understanding of the signals required to maintain a mature beta-cell phenotype may help improve the efficacy of islet transplantation.
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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.