详细记录  
题名:Apoptosis rate and transcriptional response of pancreatic islets exposed to the PPAR gamma agonist Pioglitazone.
作者:LAMOUNIER RN; COIMBRA CN; WHITE P; COSTAL FL; OLIVEIRA LS; GIANNELLA-NETO D; KAESTNER KH; CORREA-GIANNELLA ML;
来源:Diabetol Metab Syndr. 2013 Jan 8;5(1):1. doi: 10.1186/1758-5996-5-1. [ IF= 0.00 ] ]
URL :10.1186/1758-5996-5-1
日期:20130131
摘要:To explore the molecular pathways underlying thiazolidinediones effects on
pancreatic islets in conditions mimicking normo- and hyperglycemia, apoptosis
rate and transcriptional response to Pioglitazone at both physiological and
supraphysiological glucose concentrations were evaluated. Adult rat islets were
cultured at physiological (5.6 mM) and supraphysiological (23 mM) glucose
concentrations in presence of 10 muM Pioglitazone or vehicle. RNA expression
profiling was evaluated with the PancChip 13k cDNA microarray after 24-h, and
expression results for some selected genes were validated by qRT-PCR. The effects
of Pioglitazone were investigated regarding apoptosis rate after 24-, 48- and
72-h. At 5.6 mM glucose, 101 genes were modulated by Pioglitazone, while 1,235
genes were affected at 23 mM glucose. Gene networks related to lipid metabolism
were identified as altered by Pioglitazone at both glucose concentrations. At 23
mM glucose, cell cycle and cell death pathways were significantly regulated as
well. At 5.6 mM glucose, Pioglitazone elicited a transient reduction in islets
apoptosis rate while at 23 mM, Bcl2 expression was reduced and apoptosis rate was
increased by Pioglitazone. Our data demonstrate that the effect of Pioglitazone
on gene expression profile and apoptosis rate depends on the glucose
concentration. The modulation of genes related to cell death and the increased
apoptosis rate observed at supraphysiological glucose concentration raise
concerns about Pioglitazone's direct effects in conditions of hyperglycemia and
reinforce the necessity of additional studies designed to evaluate TZDs effects
on the preservation of beta-cell function in situations where glucotoxicity might
be more relevant than lipotoxicity.

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