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Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations

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Bensellam, Mohammed [UCL] Van Lommel, L. [UCL] Overbergh, L. Schuit, F. C. [UCL] Jonas, Jean-Christophe [UCL]

AIMS/HYPOTHESIS: Survival and function of insulin-secreting pancreatic beta cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2 mmol/l glucose improves rodent beta cell survival and function, whereas glucose concentrations above 10 mmol/l are deleterious. METHODS: To identify the mechanisms of such beta cell plasticity, we tested the effects of 18 h culture at 2, 5, 10 and 30 mmol/l glucose on the transcriptome of rat islets pre-cultured for 1 week at 10 mmol/l glucose using Affymetrix Rat 230 2.0 arrays. RESULTS: Culture in either 2-5 or 30 mmol/l instead of 10 mmol/l glucose markedly impaired beta cell function, while little affecting cell survival. Of about 16,000 probe-sets reliably detected in islets, some 5,000 were significantly up- or downregulated at least 1.4-fold by glucose. Analysis of these probe-sets with GeneCluster software identified ten mRNA profiles with unidirectional up- or downregulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mmol/l glucose. It also identified eight complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10 mmol/l glucose. Analysis of genes belonging to these various clusters using Onto-express and GenMAPP software revealed several signalling and metabolic pathways that may contribute to induction of beta cell dysfunction and apoptosis after culture in low- or high- vs intermediate-glucose concentration. CONCLUSIONS/INTERPRETATION: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understand the mechanisms by which glucose affects beta cell survival and function under states of chronic hypo- or hyperglycaemia.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2009
Journal information "Diabetologia : clinical and experimental diabetes and metabolism" - Vol. 52, no. 3, p. 463-476 (2009)
Peer reviewed yes
Publisher Springer (Heidelberg)
issn 0012-186X
e-issn 1432-0428
Publication status Publié
Affiliations UCL - MD/FSIO - Département de physiologie et pharmacologie
UCL - (SLuc) Service d'endocrinologie et de nutrition
MESH Subject Rats, Wistar ; Rats ; RNA, Messenger - genetics ; Nucleic Acid Hybridization ; Male ; Kinetics ; Islets of Langerhans - cytology - drug effects - physiology ; Insulin - genetics ; Glucose - pharmacology ; Glucagon - genetics ; Gene Expression Profiling ; Cluster Analysis ; Cell Survival ; Cell Culture Techniques ; Animals
Keywords Apoptosis ; Beta cell ; Cluster analysis ; Endoplasmic reticulum stress response ; Phenotypic plasticity
Links
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Bibliographic reference Bensellam, Mohammed ; Van Lommel, L. ; Overbergh, L. ; Schuit, F. C. ; Jonas, Jean-Christophe. Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations. In: Diabetologia : clinical and experimental diabetes and metabolism, Vol. 52, no. 3, p. 463-476 (2009)
Permanent URL http://hdl.handle.net/2078.1/20964