Thyroid hormone receptor TRbeta1 mediates Akt activation by T3 in pancreatic beta 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 beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1. The phosphorylation of Akt was T3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the phosphatidylinositol 3 kinase (PI3K) p85alpha subunit and the thyroid receptor beta1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a 'cytoplasmic TRbeta1' was implicated. Moreover, we evidenced that T3 treatment was able to induce kinase activity of the TRbeta1-associated PI3K. The silencing of TRbeta1 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 beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells.
Verga Falzacappa
Cecilia
C
Chair of Endocrinology, II Faculty of Medicine, University La Sapienza, Rome, Italy.
Petrucci
Eleonora
E
Patriarca
Valentina
V
Michienzi
Simona
S
Stigliano
Antonio
A
Brunetti
Ercole
E
Toscano
Vincenzo
V
Misiti
Silvia
S
D045744:Cell Line, Tumor; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology*
D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D051057:Proto-Oncogene Proteins c-akt