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

Xiangqian LI; Lina WANG; Mengjun ZHANG; Xiaoling CHEN; Li WANG

doi:10.16016/j.1000-5404.202011146

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

Basic Medicine | 更新时间：2026-01-09

- Effect of high glucose environment on transcriptome expression profile of islet β cell line
- Journal of Third Military Medical University Vol. 43, Issue 7, Pages: 584-592(2021)
- 作者机构：
  
  1.400038 重庆，陆军军医大学（第三军医大学）：基础医学院全军免疫学研究所
  2.400038 重庆，陆军军医大学（第三军医大学）：药学与检验医学系药物分析学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81871301)
- DOI：10.16016/j.1000-5404.202011146
  CLC： R322.57;R363.13;R394.3
- Received：16 November 2020，
  
  Revised：2021-01-13，
  
  Published：15 April 2021
- 稿件说明：
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Xiangqian LI, Lina WANG, Mengjun ZHANG, et al. Effect of high glucose environment on transcriptome expression profile of islet β cell line[J]. Journal of Third Military Medical University, 2021, 43(7): 584-592.
DOI：

Xiangqian LI, Lina WANG, Mengjun ZHANG, et al. Effect of high glucose environment on transcriptome expression profile of islet β cell line[J]. Journal of Third Military Medical University, 2021, 43(7): 584-592. DOI： 10.16016/j.1000-5404.202011146.

摘要

目的

研究高浓度葡萄糖刺激因素对1型糖尿病（type 1 diabetes

T1D）模型小鼠来源的胰岛β细胞系全转录组表达谱的影响，探讨高糖环境因素参与T1D发病的可能机制。

方法

将处于对数生长期的非肥胖糖尿病（non-obese diabetic

NOD）小鼠来源的胰岛β细胞系NIT-1细胞分为对照组（NIT1）和高糖处理组（HG），采用RNA-Seq技术进行全转录组测序，获取差异表达基因（differentially expressed genes

DEGs），并对DEGs进行GO注释以及KEGG Pathway富集性分析。

结果

NIT1组和HG组之间共检测到DEGs 5 548个；其中HG组上调DEGs 2 701个，下调DEGs 2 847个，其中上调DEGs显著富集在内质网应激、内质网蛋白加工处理、泛素化介导的蛋白质降解、自噬、凋亡等途径；下调基因主要富集在核糖体、代谢、生物合成、细胞周期、DNA复制等途径。HG组部分关键T1D自身抗原的mRNA表达显著增加。

结论

高糖诱导胰岛β细胞系全转录组显著变化，表现出胰岛β细胞自身抗原的表达及抗原加工、处理能力增强，提示高糖因素可能与诱导β细胞自身免疫反应及T1D的发生、发展有关。

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.

关键词

Keywords

references

DIMEGLIO L A, EVANS-MOLINA C, ORAM R A.Type 1 diabetes[J]. Lancet, 2018, 391(10138): 2449-2462. DOI:10.1016/s0140-6736(18)31320-5.

POCIOT F, LERNMARK Å. Genetic risk factors for type 1 diabetes[J]. Lancet, 2016, 387(10035): 2331-2339. DOI:10.1016/s0140-6736(16)30582-7.

ESPOSITO S, TONI G, TASCINI G, et al . Environmental factors associated with type 1 diabetes[J ] . Front Endocrinol, 2019, 10: 592. DOI:10.3389/fendo.2019.00592.

BROZZI F, NARDELLI T R, LOPES M, et al . Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms[J ] . Diabetologia, 2015, 58(10): 2307-2316. DOI:10.1007/s00125-015-3669-6.

LAMB M M, FREDERIKSEN B, SEIFERT J A, et al . Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young[J ] . Diabetologia, 2015, 58(9): 2027-2034. DOI:10.1007/s00125- 015-3657-x.

BACK S H, KAUFMAN R J. Endoplasmic reticulum stress and type 2 diabetes[J]. Annu Rev Biochem, 2012, 81(1): 767-793. DOI:10.1146/annurev- biochem-072909-095555.

COCK P J A, FIELDS C J, GOT O N, et al . The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants[J ] . Nucleic Acids Res, 2010, 38(6): 1767-1771. DOI:10.1093/nar/gkp1137.

KIM D, LANGMEAD B, SALZBERG S L.HISAT: a fast spliced aligner with low memory requirements[J]. Nat Methods, 2015, 12(4): 357-360. DOI:10.1038/nmeth.3317.

LOVE M I, HUBER W, ANDERS S.Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2[J]. Genome Biol, 2014, 15(12): 550. DOI:10.1186/s13059-014-0550-8.

LENNON G P, BETTINI M, BURTON A R, et al . T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event[J ] . Immunity, 2009, 31(4): 643-653. DOI:10.1016/j.immuni.2009.07.008.

BJÖRK E, KÄMPE O, KARLSSON F A, et al . Glucose regulation of the autoantigen GAD65 in human pancreatic islets[J ] . J Clin Endocrinol Metab, 1992, 75(6): 1574-1576. DOI:10.1210/jcem.75.6.1464667.

SKOWERA A, ELLIS R J, VARELA-CALVIÑO R, et al . CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regul ated preproinsulin epitope[J ] . J Clin Investig, 2008, 118(10): 3390-3402. DOI:10.1172/JCI35449.

WEI J J, YEWDELL J W.Peptide secretion triggers diabetes[J]. Nature, 2018, 560(7716): 33-34. DOI:10.1038/d41586-018-05710-z.

MOHAN J F, LEVISETTI M G, CALDERON B, et al . Unique autoreactive T cells recognize insulin peptides generated within the islets of Langerhans in autoimmune diabetes[J ] . Nat Immunol, 2010, 11(4): 350-354. DOI:10.1038/ni.1850.

FERRIS S T, CARRERO J A, UNANUE E R.Antigen presentation events during the initiation of autoimmune diabetes in the NOD mouse[J]. J Autoimmun, 2016, 71: 19-25. DOI:10.1016/j.jaut.2016.03.007.

STADINSKI B D, DELONG T, REISDORPH N, et al . Chromogranin A is an autoantigen in type 1 diabetes[J ] . Nat Immunol, 2010, 11(3): 225-231. DOI:10.1038/ni.1844.

ENGIN F.ER stress and development of type 1 diabetes[J]. J Investig Med, 2016, 64(1): 2-6. DOI:10.1097/JIM.0000000000000229.

SHALEV A. Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell[J]. Mol Endocrinol, 2014, 28(8): 1211-1220. DOI: 10.1210/me.2014-1095.

MARRÉ M L, JAMES E A, PIGANELLI J D. Β cell ER stress and the implications for immunogenicity in type 1 diabetes[J]. Front Cell Dev Biol, 2015, 3: 67. DOI:10.3389/fcell.2015.00067.

MARRÉ M L, PIGANELLI J D.Environmental factors contribute to β cell endoplasmic Reticulum stress and neo-antigen formation in type 1 diabetes[J]. Front Endocrinol, 2017, 8: 262. DOI:10.3389/fendo.2017.00262.

BLUESTONE J A, HEROLD K, EISENBARTH G.Genetics, pathogenesis and clinical interventions in type 1 diabetes[J]. Nature, 2010, 464(7293): 1293-1300. DOI:10.1038/nature08933.

LAM-TSE W K, LERNMARK A, DREXHAGE H A.Animal models of endocrine/organ-specific autoimmune diseases: do they really help us to understand human autoimmunity?[J]. Springer Semin Immunopathol, 2002, 24(3): 297-321. DOI: 10.1007/s00281-002-0110-2.

THOMAIDOU S, ZALDUMBIDE A, ROEP B O. Islet stress, degradation and autoimmunity[J]. Diabetes Obes Metab, 2018, 20(Suppl 2): 88-94. DOI:10.1111/dom.13387.

MONDANELLI, G, ALBINI E, PALLOTTA M T, et al , The proteasome inhibitor bortezomib controls indoleamine 2, 3-dioxygenase 1 breakdown and restores immune regulation in autoimmune diabetes[J ] . Front Immunol, 2017, 8: 428. DOI: 10.3389/fimmu.2017.00428. eCollection 2017.

EBSTEIN F, TEXTORIS-TAUBE K, KELLER C, et al . Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes[J ] . Sci Rep, 2016, 6: 24032. DOI:10.1038/srep24032.

BERKERS C R, DE JONG A, SCHUURMAN K G, et al . Peptide splicing in the proteasome creates a novel type of antigen with an isopeptide linkage[J ] . J Immunol, 2015, 195(9): 4075-4084. DOI:10.4049/jimmunol.1402454.

FIERABRACCI A. The putative role of proteolytic pathways in the pathogenesis of type 1 diabetes mellitus: the 'autophagy' hypothesis[J]. Med Hypotheses, 2014, 82(5): 553-557. DOI: 10.1016/j.mehy.2014.02.010.

SCHMID D, PYPAERT M, MVNZ C. Antigen-loading compartments for major histocompatibility complex class Ⅱ molecules continuously receive input from autophagosomes[J]. Immunity, 2007, 26(1): 79-92. DOI:10.1016/j.immuni.2006.10.018.

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