Thyroid hormone receptor TRβ1 mediates Akt activation by T3 in pancreatic β cells

It has recently been recognized that thyroid hormones may rapidly generate biological responses by non-genomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways underlying these effects are just beginning to be defined. We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic b cells rRINm5F and hCM via thyroid hormone receptor (TR) b1. The phosphorylation of Akt was T3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the phosphatidylinositol 3 kinase (PI3K) p85a subunit and the thyroid receptor b1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a ‘cytoplasmic TRb1’ was implicated. Moreover, we evidenced that T3 treatment was able to induce kinase activity of the TRb1-associated PI3K. The silencing of TRb1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt. This action involved a T3-induced nuclear translocation of activated Akt, as demonstrated by confocal immunofluorescence. In summary, T3 is able to specifically activate Akt in the islet b cells rRINm5F and hCM through the interaction between TRb1 and PI3K p85a, demonstrating the involvement of TRb1 in this novel T3 non-genomic action in islet b cells.