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 T-3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta 1. The phosphorylation of Akt was T-3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the phosphaticlylinositol 3 kinase (PI3K) p85 alpha subunit and the thyroid receptor beta 1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a 'cytoplasmic TR beta 1' was implicated. Moreover, we evidenced that T-3 treatment was able to induce kinase activity of the TR beta 1 -associated PI3K. The silencing of TR beta 1 expression through RNAi confirmed this receptor to be crucial for the T-3-induced activation of Akt. This action involved a T-3-induced nuclear translocation of activated akt, as demonstrated by confocal immunofluorescence. In summary, T-3 is able to specifically activate Akt in the islet 0 cells rRINm5F and hCM through the interaction between TR beta 1 and PI3K p85a, demonstrating the involvement of TR beta 1 in this novel T-3 non-genomic action in islet beta cells.