Abstract
This study is to identify the circular RNA (circRNA) expression profile that is functionally related to pancreatic islet β-cell autophagy and their potential regulation mechanisms in type 2 diabetes mellitus (T2DM). T2DM rat model was constructed by administration of high-fat and high-sugar diet. β-cells were isolated from islets by flow cytometry. CircRNA expression profile in β-cells was detected by circRNA microarrays, and the differentially expressed circRNAs were identified and validated by qRT-PCR. MicroRNA (miRNA) target prediction software and multiple bioinformatic approaches were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. A total of 825 differentially expressed circular transcripts were identified in T2DM rats compared with control rats, among which 388 were upregulated and 437 were downregulated. Ten circRNAs were identified to have significant differences by qRT-PCR. GO analysis enriched terms such as organelle membrane and protein binding and the top enriched pathways for the circRNAs included MAPK signaling pathway. The differentially expressed circRNAs might involve in MAPK signaling pathway, apoptosis, and Ras signaling pathway. We speculate that these circRNAs, especially rno_circRNA_008565, can regulate the autophagy of islet β-cells via interactions with miRNA. Dysregulation of several circRNAs may play a role in T2DM development, and rno_circRNA_008565 may be a potential regulator of β-cell autophagy.
Highlights
Diabetes is one of the chronic noninfectious diseases that threaten human health worldwide
Because of the aging population, the prevalence of bad lifestyle, and the change of dietary structure, type 2 diabetes mellitus (T2DM) shows a rapid increase in China. e prevalence rate of adult diabetes in China was 5.49% in 2000-2001 [1], which has been increased to 11.6% in 2010 [2]. e latest research shows that the incidence of T2DM in adults is as high as 11.6% [2], which is expected to increase [3]
High-throughput microarray was used to determine circRNA expression in islet β-cells from control and T2DM groups of rats
Summary
Diabetes is one of the chronic noninfectious diseases that threaten human health worldwide. Because of the aging population, the prevalence of bad lifestyle, and the change of dietary structure, type 2 diabetes mellitus (T2DM) shows a rapid increase in China. E prevalence rate of adult diabetes in China was 5.49% in 2000-2001 [1], which has been increased to 11.6% in 2010 [2]. E latest research shows that the incidence of T2DM in adults is as high as 11.6% [2], which is expected to increase [3]. Autophagy is one of the self-protection mechanisms of islet β-cells [5]. After knocking out ATG7 in mouse islet β-cells, the mice showed impaired glucose tolerance, decreased serum insulin levels, and increased apoptosis while decreased proliferation of islet β-cells [8]
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