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Title: Persistent or transient human β cell dysfunction induced by metabolic stress : specific signatures and shared gene expression with type 2 diabetes
Authors: Marselli, Lorella
Piron, Anthony
Suleiman, Mara
Colli, Maikel L.
Yi, Xiaoyan
Khamis, Amna
Carrat, Gaelle R.
Rutter, Guy A.
Bugliani, Marco
Giusti, Laura
Ronci, Maurizio
Ibberson, Mark
Turatsinze, Jean-Valery
Boggi, Ugo
de Simone, Paolo
de Tata, Vincenzo
Lopes, Miguel
Nasteska, Daniela
de Luca, Carmela
Tesi, Marta
Bosi, Emanuele
Singh, Pratibha
Campani, Daniela
Schulte, Anke M.
Solimena, Michele
Hecht, Peter
Rady, Brian
Bakaj, Ivona
Pocai, Alessandro
Norquay, Lisa
Thorens, Bernard
Canouil, Mickaël
Froguel, Philippe
Eizirik, Decio L.
Cnop, Miriam
Marchetti, Piero
Keywords: Science::Medicine
Issue Date: 2020
Source: Marselli, L., Piron, A., Suleiman, M., Colli, M. L., Yi, X., Khamis, A., . . . Marchetti, P. (2020). Persistent or transient human β cell dysfunction induced by metabolic stress : specific signatures and shared gene expression with type 2 diabetes. Cell Reports, 33(9), 108466-. doi:10.1016/j.celrep.2020.108466
Journal: Cell Reports 
Abstract: Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies.
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108466
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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