Apoptosis rate and transcriptional response of pancreatic islets exposed to the PPAR gamma agonist Pioglitazone

Autor(es)

Lamounier, Rodrigo N. ^{[1, 2, 3]} ; Coimbra, Cassio N. ^{[1, 4]} ; White, Peter ^{[2, 3]} ; Costal, Flavia L. ^[1] ; Oliveira, Leonardo S. ^{[1, 4]} ; Giannella-Neto, Daniel ^[5] ; Kaestner, Klaus H. ^{[2, 3]} ; Correa-Giannella, Maria Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Cellular & Mol Endocrinol LIM 25, Sch Med, BR-01246903 Sao Paulo - Brazil

^[2] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 - USA

^[3] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 - USA

^[4] Univ Santo Amaro, Sao Paulo - Brazil

^[5] Univ Nove Julho UNINOVE, Postgrad Program Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DIABETOLOGY & METABOLIC SYNDROME; v. 5, JAN 8 2013.
• Citações Web of Science: 3

Resumo

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 mu M 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. (AU)

• Processo FAPESP: 04/10797-4 - Avaliacao do efeitos diretos das tiazolidinedionas sobre as ilhotas pancreaticas murideas.
• Beneficiário: Maria Lucia Cardillo Corrêa Giannella
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/01467-0 - Efeitos das tiazolidinedionas sobre a viabilidade funcional, o índice de apoptose e a expressão de genes relacionados a apoptose em ilhotas pancreáticas murideas e humanas
• Beneficiário: Cassio Negro Coimbra
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 04/01816-5 - Perfil de expressão de genes modulados pelas tiazolidinedionas em ilhotas pancreáticas murideas e humanas
• Beneficiário: Rodrigo Nunes Lamounier
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto