ArticlePloS one2014
Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Pancreatic Stone Protein as an Emerging Biomarker in Paediatric Nosocomial and Postoperative Sepsis: An Integrative Review of Diagnostic and Prognostic Performance.International journal of molecular sciences · 2026Review
- Single-nucleus RNA sequencing reveals the effects of key regulators on human pancreatic adenocarcinoma and its tumor microenvironment.Journal of gastrointestinal oncology · 2026Article
- Evidence for a Pro-Inflammatory State of Macrophages from Non-Obese Type-2 Diabetic Goto-Kakizaki Rats.International journal of molecular sciences · 2024Article
- Upregulation ofInternational journal of molecular sciences · 2022Article
- Alternative exon splicing and differential expression in pancreatic islets reveals candidate genes and pathways implicated in early diabetes development.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular CaProceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Article
- The Role of Intestinal C-type Regenerating Islet Derived-3 Lectins for Nonalcoholic Steatohepatitis.Hepatology communications · 2018Article
- Improved Serial Sectioning Techniques for Correlative Light-Electron Microscopy Mapping of Human Langerhans Islets.Acta histochemica et cytochemica · 2018Article
- Role of regenerating gene IA expression on local invasion and survival in nasopharyngeal carcinoma.Biological research · 2017Article
- Article
- Expression of REG Iα gene in type 2 diabetics in Pakistan.Diabetology & metabolic syndrome · 2015Article
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regenerating (REG) proteins are associated with islet development, β-cell damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are involved in cell growth/survival and/or inflammation and the Reg1 promoter contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2 diabetes, overexpress Reg1, 3α, 3β and 3γ, vs Wistar islets. Goto-Kakizaki rat islets also exhibit increased cytokine/chemokine expression/release, particularly IL-6. Here we analyzed Reg1 and Reg3β expression and REG-1 immuno-localization in the GK rat pancreas in relationship with inflammation. Isolated pancreatic islets and acinar tissue from male adult Wistar and diabetic GK rats were used for quantitative RT-PCR analysis. REG-1 immunohistochemistry was performed on paraffin sections with a monoclonal anti-rat REG-1 antibody. Islet cytokine/chemokine release was measured after 48 h-culture. Islet macrophage-positive area was quantified on cryostat sections using anti-CD68 and major histocompatibility complex (MHC) class II antibodies. Pancreatic exocrine-to-endocrine Reg1 and Reg3β mRNA ratios were markedly increased in Wistar vs GK rats. Conversely, both genes were upregulated in isolated GK rat islets. These findings were unexpected, because Reg genes are expressed in the pancreatic acinar tissue. However, we observed REG-1 protein labeling in acinar peri-ductal tissue close to islets and around large, often disorganized, GK rat islets, which may retain acinar cells due to their irregular shape. These large islets also showed peri-islet macrophage infiltration and increased release of various cytokines/chemokines, particularly IL-6. Thus, IL-6 might potentially trigger acinar REG-1 expression and secretion in the vicinity of large diabetic GK rat islets. This increased acinar REG-1 expression might reflect an adaptive though unsuccessful response to deleterious microenvironment.
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