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

ABSTRACT: Background: Survival and function of insulin-secreting pancreatic β-cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2mM glucose improves rodent β-cell survival and function whereas glucose concentrations above 10mM are deleterious. Aim-Method: To identify the mechanisms of such β-cell plasticity, we tested the effects of a 18h culture at 2, 5, 10 and 30mM glucose on the transcriptome of rat islets precultured for 1 week at 10mM glucose (Affymetrix Rat 230.2 arrays). Results: Culture in either 2-5mM or 30mM instead of 10mM glucose markedly impaired β-cell function without affecting islet cell survival. Of ~16000 probe sets reliably detected in islets, ~5000 were significantly regulated at least 1.4-fold by glucose. Analysis of these probe sets with GeneCluster software identified 10 mRNA profiles with unidirectional up- or down-regulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mM glucose, and 8 complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10mM glucose. Analysis of genes belonging to these various clusters with Onto-express and GenMapp software revealed several signaling and metabolic pathways that may contribute to the induction of β-cell dysfunction and apoptosis after culture in low or high vs. intermediate glucose concentration. Conclusion: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understanding the mechanisms by which glucose affects β-cell survival and function under states of chronic hypo- or hyperglycemia. Keywords: Dose response

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE12817 | GEO | 2009/01/26

SECONDARY ACCESSION(S): PRJNA111125

REPOSITORIES: GEO