Triiodothyronine (T3) Induces Proinsulin Gene Expression by Activating PI3K: Possible Roles for GSK-3 beta and the Transcriptional Factor PDX-1

Autor(es)

Goulart-Silva, F. ^{[1, 2]} ; Serrano-Nascimento, C. ^[1] ; Texeira, S. S. ^[1] ; Nunes, M. T. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Univ Estadual Londrina, Dept Physiol Sci, BR-86051990 Londrina, PR - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES; v. 121, n. 1, p. 14-19, JAN 2013.
• Citações Web of Science: 1

Resumo

Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH effects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3 beta signaling pathway, and a transcriptional factor for insulin (PDX-1). INS-1E cells were sorted into 3 groups: control and TH-depleted treated or not with T3 for 30 min. Cells were also previously treated with actinomycin D (ActD), cycloheximide (CHX), wortmannin or Akt inhibitor. Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3 beta and PDX-1 protein content was analyzed by Western blotting. TH depletion decreased proinsulin mRNA content, which was restored after acute T3 treatment. ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory effect of T3 on proinsulin mRNA expression. TH depletion did not affect the phosphorylated GSK-3 beta and PDX-1 protein content; but T3 treatment led to an increase in the content of these proteins. These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3 beta by phosphorylation. Since GSK-3 beta enhances PDX-1 degradation rate, the GSK-3 beta inactivation could explain the increase of PDX-1 content in T3-treated cells. Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. (AU)

• Processo FAPESP: 08/56446-9 - Analise molecular das acoes pos-transcricionais dos hormonios tiroideanos nas celulas beta pancreaticas e suas repercussoes sobre a sintese e secrecao de insulina
• Beneficiário: Francemilson Goulart da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado