Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

• Published in: International journal of molecular sciences Vol. 20; no. 23; p. 5903
• Main Authors: Krishnan, Preethi, Syed, Farooq, Jiyun Kang, Nicole, Mirmira, Raghavendra G, Evans-Molina, Carmella
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.11.2019; MDPI
• Subjects: Apoptosis; Beta cells; Biomarkers; Cadavers; Calcium signalling; Cytokines; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - pathology; Exosomes; Exosomes - genetics; Gene expression; Gene Expression Profiling; Genetic Markers; Heterogeneity; Humans; IL-1β; Inflammation; Insulin; Insulin secretion; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; MicroRNAs - genetics; Necrosis; Pancreas; Pathogenesis; Proteins; RNA - analysis; RNA - genetics; RNA, Long Noncoding - genetics; RNA, Messenger - genetics; RNA, Small Untranslated - genetics; Sequence Analysis, RNA - methods; Signal Transduction; γ-Interferon; islet-derived exosomes; long noncoding RNA; total RNA sequencing; mRNA; small noncoding RNA; small RNA sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20235903

Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a -value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.