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Title

Microarray analysis of isolated human islet transcriptome in type 2 diabetes and the role of the ubiquitin-proteasome system in pancreatic beta cell dysfunction

Authors
Liechti, Robin
Cheon, Hwanju
Suleiman, Mara
Marselli, Lorella
Filipponi, Franco
Boggi, Ugo
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Published in Molecular and Cellular Endocrinology. 2013, vol. 367, no. 1-2, p. 1-10
Abstract To shed light on islet cell molecular phenotype in human type 2 diabetes (T2D), we studied the transcriptome of non-diabetic (ND) and T2D islets to then focus on the ubiquitin-proteasome system (UPS), the major protein degradation pathway. We assessed gene expression, amount of ubiquitinated proteins, proteasome activity, and the effects of proteasome inhibition and prolonged exposure to palmitate. Microarray analysis identified more than one thousand genes differently expressed in T2D islets, involved in many structures and functions, with consistent alterations of the UPS. Quantitative RT-PCR demonstrated downregulation of selected UPS genes in T2D islets and beta cell fractions, with greater ubiquitin accumulation and reduced proteasome activity. Chemically induced reduction of proteasome activity was associated with lower glucose-stimulated insulin secretion, which was partly reproduced by palmitate exposure. These results show the presence of many changes in islet transcriptome in T2D islets and underline the importance of the association between UPS alterations and beta cell dysfunction in human T2D.
Keywords AgedAnimalsCell LineDiabetes Mellitus, Type 2/genetics/pathology/physiopathologyFemaleGene Expression ProfilingGene Expression Regulation/drug effectsHumansImmunohistochemistryInsulin/secretionInsulin-Secreting Cells/drug effects/metabolism/pathology/secretionMaleMiddle AgedOligonucleotide Array Sequence AnalysisPalmitates/pharmacologyProteasome Endopeptidase Complex/genetics/metabolismProteasome Inhibitors/pharmacologyRatsReverse Transcriptase Polymerase Chain ReactionTranscriptome/geneticsUbiquitin/genetics/metabolismUbiquitinated Proteins/genetics/metabolism
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PMID: 23246353
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BUGLIANI, Marco et al. Microarray analysis of isolated human islet transcriptome in type 2 diabetes and the role of the ubiquitin-proteasome system in pancreatic beta cell dysfunction. In: Molecular and Cellular Endocrinology, 2013, vol. 367, n° 1-2, p. 1-10. https://archive-ouverte.unige.ch/unige:40335

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Deposited on : 2014-09-18

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