ArticleDiabetologia2022
Lipotoxicity-induced circGlis3 impairs beta cell function and is transmitted by exosomes to promote islet endothelial cell dysfunction.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Adipocyte-derived exosomal ANGPTL2 promotes beta cell dysfunction via the EIF2α/ATF4/CHOP stress pathway in mice.Diabetologia · 2026Article
- Circular RNAs in obesity and related metabolic disorders: mechanistic insights and therapeutic perspectives.Frontiers in genetics · 2026Review
- Circular RNAs in diabetes mellitus and its complications: a systematic review and in silico analyses.Endocrine connections · 2025Article
- Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease.Diabetes & metabolism journal · 2025Review
- Emerging role and clinical applications of circular RNAs in human diseases.Functional & integrative genomics · 2025Review
- The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases.International journal of molecular sciences · 2025Review
- Circular RNAs in human diseases.MedComm · 2024Review
- Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response.International journal of molecular sciences · 2024Article
- The systematic role of pancreatic cancer exosomes: distant communication, liquid biopsy and future therapy.Cancer cell international · 2024Review
- circGlis3 promotes β-cell dysfunction by binding to heterogeneous nuclear ribonucleoprotein F and encoding Glis3-348aa protein.iScience · 2024Article
- MIB2 promotes the progression of non-small cell lung cancer by regulating cell cycle control pathways.Genes & genomics · 2023Article
- Endoplasmic reticulum stress: a novel targeted approach to repair bone defects by regulating osteogenesis and angiogenesis.Journal of translational medicine · 2023Review
- Article
- Role of Circulating Exosomal miRNA-3976 in Early Diabetic Retinopathy.International journal of nanomedicine · 2023Article
- Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes.Frontiers in immunology · 2023Article
- Mutated lncRNA increase the risk of type 2 diabetes by promoting β cell dysfunction and insulin resistance.Cell death & disease · 2022Article
- Review
- Exosomal RNAs: Novel Potential Biomarkers for Diseases-A Review.International journal of molecular sciences · 2022Review
- Circular RNAs in diabetes and its complications: Current knowledge and future prospects.Frontiers in genetics · 2022Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisLipotoxicity constitutes the major driving force for type 2 diabetes. Circular RNAs (circRNAs) play important roles in regulating beta cell function and exosomes are essential mediators of intercellular communication. The role of exosomal circRNAs in type 2 diabetes remains largely unknown. We aimed to examine whether lipotoxicity induces dysregulation of circRNAs in beta cell-derived exosomes and to determine the contribution of exosomal circRNAs to the development of type 2 diabetes.
methodsExosomes were extracted from MIN6 cells treated with palmitate or BSA, and RNA sequencing was performed. CircGlis3 (Gli-similar 3) expression level was validated by qPCR. The impact of circGlis3 on beta cell function and the deleterious effects of exosomal circGlis3 on islet endothelial cells (islet ECs) were investigated in vitro and in vivo in human and mouse models by gain or loss of function assays. The molecular mechanism of circGlis3 was explored by RNA pull-down and immunoprecipitation assays.
resultsBeta cell-derived exosomal circGlis3 was significantly upregulated under lipotoxic conditions, and exosomal circGlis3 levels were also elevated in the serum of mouse models of diabetes and participants with type 2 diabetes. CircGlis3 participated in lipotoxicity-induced beta cell dysfunction in vitro and in vivo. Moreover, beta cell-derived exosomal circGlis3 could be transferred to islet ECs and reduce the cell viability, cell migration and angiogenesis of islet ECs. Mechanistically, circGlis3 promoted the degradation of glucocorticoid modulatory element-binding protein 1 (GMEB1) by facilitating the interaction between GMEB1 and mindbomb E3 ubiquitin protein ligase 2 (MIB2), thus suppressing the phosphorylation of heat shock protein 27 (HSP27). CONCLUSIONS/
interpretationOur study points to the involvement of circGlis3 in diabetes development, and exosomal circGlis3 transfer as a communication mode between beta cells and islet ECs, suggesting that circGlis3 might be a potential biomarker and therapeutic target for type 2 diabetes. DATA AVAILABILITY: The RNA-sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) database, with accession number PRJNA689673. Mass spectrometry data are available via ProteomeXchange with identifier PXD024693.
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