ECE2006 Oral Communications ThyroidOC57 British Thyroid Association Award (8 abstracts)
Thyroid hormone receptor TRβ1 mediates Akt activation by T3 in pancreatic β cells
SM Misiti 1 , CV VergaFalzacappa 1 , VP Patriarca 1 , SM Michienzi 1 , AS Stigliano 1 , EB Brunetti 2 & VT Toscano 1
1University of Rome La Sapienza II Faculty of Medicine, Roma, Italy; 2S. Peter Hospital FbF AFaRR, Roma, Italy.
Background: It has recently been recognized that thyroid hormones may rapidly generate biological responses by nongenomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways for these effects are just beginning to be defined.
Aim: To examine the specific pathway via which T3 can activate Akt in pancreatic beta cells and to understand further the possible implication of a nongenomic action of T3 in these cellular systems.
Results: We demonstrated that thyroid hormone T3 rapidly induces phosphorylation of Akt in vitro in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor β1. The T3-dependent phosphorylation of Akt was blocked by PI3K inhibitor and by the T3 analog BPA, indicating the effect to be T3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the PI3K p85α subunit and the thyroid receptor β1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a ‘cytoplasmic TRβ1’ was implicated. The silencing of TRβ1 expression through RNAi confirmed this receptor to be crucial for the T3 induced activation of Akt. This action involved a T3-induced cytoplasmic recruitment of Akt and the consequent nuclear translocation of activated Akt as demonstrated by confocal immunofluorescence.
Conclusion: T3 is able to specifically activate Akt in the islet beta cell lines rRINm5F and hCM through the interaction of TRβ1 and PI3Kp85α, demonstrating the involvement of TRβ1 in this novel T3-nongenomic action in islet beta cells.
Volume 11
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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