Page 63 - 76_03

An. R. Acad. Nac. Farm., 2010, 76 (3): 357-377

ARTÍCULO

TSC1-TSC2 complex on the crossroad of pancreatic
ß cell signaling. Role on cell proliferation, death
and survival

Alberto Bartolomé1,2,3, Carlos Guillén1,2,3, Manuel Benito1,2,*

1 Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia,
Universidad Complutense de Madrid, Spain.
2 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades
Metabólicas Asociadas (CIBERDEM).
3 These authors contributed equally to this work.
Trabajo galardonado con el Premio FAES Farma 2009 del Concurso Científico
de la RANF.
Recibido el 4 de junio de 2010.

ABSTRACT

TSC1-TSC2 complex has emerged as a signal interaction core
within the cell. This complex integrates both nutrient and growth
factor signaling and is a critical negative regulator of mTORC1.
mTORC1 signaling leads to increased protein biosynthesis, which is
essential for cell proliferation. Other cellular events such as endo-
plasmic reticulum stress and authophagy are intimately linked with
TSC/mTORC1 pathway and play an important role in pancreatic ß
cell death or survival. We found that either insulin, glucose inde-
pendent signaling or the energetic status of the cell are able to mod-
ulate TSC2 phosphorylation in pancreatic ß cell lines. To show the
central role of TSC2 for these cells, we conducted siRNA-mediated
TSC2 silencing. Downregulation of TSC2 leads to an increase in
mTORC1/p70S6K signaling, this produces resistance to insulin ac-
tion. However, specific expression of insulin receptor isoform A re-
stored insulin signalling under these conditions. Moreover, we have

357