The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps of muscle development and growth, but the physiological relevance and the downstream effectors are under investigation. Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin. In the differentiated state, S6K1(-/-) myotubes have a normal number of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires distinct effectors for the control of muscle cell cycle and size, potentially opening new avenues of therapeutic intervention against neoplasia or muscle atrophy.

Factors that promote pancreatic β cell growth and function are potential therapeutic targets for diabetes mellitus. In mice, genetic experiments suggest that signaling cascades initiated by insulin and IGFs positively regulate β cell mass and insulin secretion. Akt and S6 kinase (S6K) family members are activated as part of these signaling cascades, but how the interplay between these proteins controls β cell growth and function has not been determined. Here, we found that although transgenic mice overexpressing the constitutively active form of Akt1 under the rat insulin promoter (RIP-MyrAkt1 mice) had enlarged β cells and high plasma insulin levels, leading to improved glucose tolerance, a substantial proportion of the mice developed insulinomas later in life, which caused decreased viability. This oncogenic transformation tightly correlated with nuclear exclusion of the tumor suppressor PTEN. To address the role of the mammalian target of rapamycin (mTOR) substrate S6K1 in the MyrAkt1-mediated phenotype, we crossed RIP-MyrAkt1 and S6K1-deficient mice. The resulting mice displayed reduced insulinemia and glycemia compared with RIP-MyrAkt1 mice due to a combined effect of improved insulin secretion and insulin sensitivity. Importantly, although the increase in β cell size in RIP-MyrAkt1 mice was not affected by S6K1 deficiency, the hyperplastic transformation required S6K1. Our results therefore identify S6K1 as a critical element for MyrAkt1-induced tumor formation and suggest that it may represent a useful target for anticancer therapy downstream of mTOR.

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al., 2009) est un instrument de mesure autorapporté de 52 ou de 28 items (pour sa version courte) qui évalue le narcissisme pathologique a `partir de deux dimensions (grandiosité et vulnérabilité) et sept facettes spécifiques. Le PNI a de bonnes qualités métrologiques et il a été utilisé dans de nombreuses études. Nous en présentons ici une version française et sa validation. Pour cette étude, on a eu recours a `1301 participants. Les résultats montrent que cette version française, tant dans sa version longue que courte, peut être considérée comme ayant de bonnes qualités métrologiques quant a `la validité de construit (analyse factorielle), la fidélité (coefficient de cohérence interne), la validité convergente (corrélations avec d'autres variables liées a `la personnalité) et la stabilité temporelle. Intérêt publicLe narcissisme est un concept psychologique a `la base de l'estime de soi, de l'identité et du concept de soi et il est susceptible de se muer en une forme pathologique. Un questionnaire récent permet d'évaluer certaines de ses composantes essentielles. Nous présentons ici la traduction et la validation en français de ce questionnaire, qui peut être utilisé en recherche comme en clinique.Mots-clés : troubles de la personnalité, narcissisme, personnalité, diagnostic.

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The objectives of this study were to develop a French version of the Pathological Narcissism Inventory (PNI ; Pincus et al., 2009) and to examine its internal structure. This French version was developed using a forward-backward procedure. Two two-person teams worked independently, one translating from English to French, the other translating back from French to English afterwards. Next, the two teams were assembled, and a new person joined them, and this committee developed the final French items on the basis of this work. The translated measure was then administrated to French speaking participants and the internal structure of this version was examined through a series of Factor Analyses. First, Confirmatory Factor Analysis (CFA) failed to reproduce the original one-level structure of the English version, as well as the two-level structure identified by Wright et al. (2012). Principal Component Analysis (PCA) was then performed to identify the internal structure of our data, which appears very similar to the English one and two-level structures. The sample was then randomly divided in two and the best fitting model was compared with PCA and CFA in the two subsamples. Finally, a multilevel model with fewer items best fits the data.

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