[Measuring the impact of a multimodal intervention on falls and the fear of falling]. / Mesure de l'impact d'une intervention multimodale sur les chutes et la peur de chuter.

Falls are common among the elderly, and can have serious consequences: fracture, hospitalization, loss of independence, institutionalization and death. However, falls are not inevitable, and they can be prevented. The "autonomy prevention" kit (Equilibr'Age workshops, occupational therapy advice) has helped to reduce the number of falls and improve people's quality of life. The program will now be rolled out to a wider public.

[Towards a better acceptance of gerontotechnologies]. / Vers une meilleure acceptation des gérontechnologies.

Gerontotechnologies are becoming increasingly important for the elderly, their relatives and the professionals who accompany them. However, this deployment raises a large number of questions, fears and reluctance - or "technoscepticism" - including in the health and medico-social sectors. There are levers that could promote the successful implementation of these technologies.

Adaptive ß-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance.

Both type 1 and type 2 diabetes are characterized by deficient insulin secretion and decreased ß-cell mass. Thus, regenerative strategies to increase ß-cell mass need to be developed. To characterize mechanisms of ß-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how ß-cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of ß-cell mass was observed during treatment up to 8 weeks. ß-Cell mass increase was partially reversible upon treatment cessation and reinduced upon subsequent treatment. ß-Cell neogenesis was suggested by an increased number of islets, mainly close to ducts, and increased Sox9 and Ngn3 mRNA levels in islets, but lineage-tracing experiments revealed that neoformed ß-cells did not derive from Sox9- or Ngn3-expressing cells. CORT treatment after ß-cell depletion partially restored ß-cells. Finally, ß-cell neogenesis was shown to be indirectly stimulated by CORT because serum from CORT-treated mice increased ß-cell differentiation in in vitro cultures of pancreatic buds. Altogether, the results present a novel model of ß-cell neogenesis in the adult mouse and identify the presence of neogenic factors in the serum of CORT-treated mice.

Fetal PGC-1α overexpression programs adult pancreatic ß-cell dysfunction.

Adult ß-cell dysfunction, a hallmark of type 2 diabetes, can be programmed by adverse fetal environment. We have shown that fetal glucocorticoids (GCs) participate in this programming through inhibition of ß-cell development. Here we have investigated the molecular mechanisms underlying this regulation. We showed that GCs stimulate the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a coregulator of the GCs receptor (GR), and that the overexpression of PGC-1α represses genes important for ß-cell development and function. More precisely, PGC-1α inhibited the expression of the key ß-cell transcription factor pancreatic duodenal homeobox 1 (Pdx1). This repression required the GR and was mediated through binding of a GR/PGC-1α complex to the Pdx1 promoter. To explore PGC-1α function, we generated mice with inducible ß-cell PGC-1α overexpression. Mice overexpressing PGC-1α exhibited at adult age impaired glucose tolerance associated with reduced insulin secretion, decreased ß-cell mass, and ß-cell hypotrophy. Interestingly, PGC-1α expression in fetal life only was sufficient to impair adult ß-cell function whereas ß-cell PGC-1α overexpression from adult age had no consequence on ß-cell function. Altogether, our results demonstrate that the GR and PGC-1α participate in the fetal programming of adult ß-cell function through inhibition of Pdx1 expression.