Journal article

Phosphoinositide 3-kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1

Sara Froejdoe, Christine Durand, Laurent Molin, Andrew L Carey, Assam El-Osta, Bronwyn A Kingwell, Mark A Febbraio, Florence Solari, Hubert Vidal, Luciano Pirola

Molecular and Cellular Endocrinology | ELSEVIER IRELAND LTD | Published : 2011


The protein deacetylase SIRT1, and its activator resveratrol, exert beneficial effects on glucose metabolism. Different SIRT1 targets have been identified, including PTP1B, AMPK, FOXO, PGC-1α and IRS2. The latter may underscore a tight link between SIRT1 and insulin signaling components. However, whether SIRT1 has a direct effect on insulin resistance and whether resveratrol acts directly or indirectly in this context is still a matter of controversy and this question has not been addressed in muscle cells. Here, we show that SIRT1 protein expression is decreased in muscle biopsies and primary myotubes derived from type 2 diabetic patients, suggesting a contribution of diminished SIRT1 in th..

View full abstract


Funding Acknowledgements

We thank Drs. B.M. Burgering (University Medical Center Utrecht, Utrecht, The Netherlands) and E. Verdin (Gladstone Institute of Virology and Immunology, University of California,) for donation of SIRT1 plasmids. We acknowledge Cyrille Debard and Graeme Lancaster for preparation and maintenance of human myotubes and discussion, respectively. Nematode strains were provided by the Caenorhabditis Genetic Center. This work was supported by INSERM (To LP, Programme National de Recherche sur le Diabete) and Association pour la Recherche contre le Cancer (to FS). SF was supported by a French University Ministry pre-doctoral fellowship. LP was partly supported by the French-Australian INSERM-NHMRC programme. AE-O, MAF and BAK are supported by NHMRC Research Fellowships.