Effect of high glucose environment on transcriptome expression profile of islet β cell line

Abstract

Objective To study the effect of high glucose concentration on the transcriptome expression profile of islet β cells derived from type 1 diabetes (T1D) mice and to explore the possible mechanism of high glucose environment in the pathogenesis of T1D. Methods The non-obese diabetic (NOD) mice-derived islet β cell line NIT-1 in logarithmic growth phase were divided into high glucose-treated (HG) and control (NIT1) group. The cells in the NIT1 group were routinely cultured in F-12K medium, while HG group were treated with 20 mmol/L glucose. Whole transcriptome profile was analyzed using RNA-sequencing technology to obtain the differentially expressed genes (DEGs). And the DEGs were further analyzed by GO annotation and KEGG pathway enrichment analysis. Results A total of 5 548 DEGs were detected between the NIT1 group and HG group. Among them, 2 701 DEGs were up-regulated in the HG group, which were significantly enriched in endoplasmic reticulum stress, endoplasmic reticulum protein processing, ubiquitin-mediated protein degradation, autophagy and apoptosis pathways. And the 2 847 down-regulated genes were mainly concentrated in ribosome, metabolism, biosynthesis, cell cycle and DNA replication. Moreover, the mRNA levels of some important T1D auto-antigens were significantly increased in the HG group. Conclusion High glucose environment significantly changes the whole-transcriptome profile of islet β cells, and promotes the abilities of antigen processing and presentation, suggesting that high glucose might be associated with the induction of autoimmune response of islet cells and the incidence and development of T1D.

Keywords

• diabetes mellitus
• high glucose
• islet β cells
• transcriptome