18 research outputs found

    Les rites du labour en Algérie

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    Servier J. Les rites du labour en Algérie. In: Journal de la Société des Africanistes, 1951, tome 21, fascicule 2. pp. 175-196

    À propos d'une enquête sociologique sur les gitans et nomades de France — Méthode et prospective

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    Servier Jean. À propos d'une enquête sociologique sur les gitans et nomades de France — Méthode et prospective. In: Ethnies, volume 1, 1971. Colloque Franco-britannique sur les relations raciales en France et en Grande-Bretagne. pp. 203-209

    Un exemple d'organisation politique traditionnelle : une tribu kabyle, les Iflissen-Lebhar

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    Servier Jean. Un exemple d'organisation politique traditionnelle : une tribu kabyle, les Iflissen-Lebhar. In: Revue de l'Occident musulman et de la Méditerranée, n°2, 1966. pp. 169-187

    L'utopie

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    128 p., ref. bib. : 2 p.1/

    Dans l'Aurès sur les pas des rebelles / Jean Servier

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    Contient une table des matièresAvec mode text

    Adieu djebels / Jean Servier

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    Contient une table des matièresAvec mode text

    High glucose-induced hypoxia may contribute to β-cell glucotoxicity

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    Background and Aim: Chronic exposure to high glucose concentrations markedly alters β-cell gene expression, function and survival, but the mechanisms of these glucotoxic effects are not fully understood. We previously reported that culture of rat islets in 30 instead of 10 mM glucose markedly increases the mRNA levels of most glycolytic enzymes and of Adrenomedullin (Adm), a specific target gene of Hypoxia Inducible Factors 1 and 2 (HIF1 and HIF2). We therefore postulated that high glucose stimulation of O2 consumption induces a moderate level of β-cell hypoxia that may contribute to β-cell glucotoxicity. Methods: Rat islets and INS1E β cells were cultured in RPMI medium containing 2, 5, 10 or 30 mM glucose (G2-G30) under normoxic (20% O2, pO2 ~151 mmHg), hypoxic (5% O2, pO2 ~38 mmHg) or hyperoxic (60% O2, pO2 ~454 mmHg) conditions. CoCl2 (10-100 µmol/l) was used as a pharmacological activator of HIF. Islets were isolated from 12 week-old diabetic db/db mice and their non diabetic db/+ littermates. HIF target gene mRNA levels were measured by real-time RT-PCR; HIF protein levels were measured by western blot; formation of pimonidazole-protein adducts during the last 2h of culture, a sensitive indicator of tissue hypoxia (pO2<10 mmHg), was measured by western blot and immunohistochemistry. Results: In vitro, the glucose stimulation of Adm expression in INS1E cells and whole rat islets was mimicked by hypoxia and CoCl2, and was prevented by hyperoxia and by pharmacological inhibition of glucose-stimulated Ca2+ influx and insulin secretion with diazoxide or nimodipine. In contrast, the glucose stimulation of Txnip and Aldob expression, two genes that are not targets of HIF, was unaffected by hypoxia, CoCl2 and hyperoxia, and was markedly enhanced by diazoxide and nimodipine. In INS1E cells, glucose concentration-dependently increased HIF1α and HIF2α protein levels (~4 fold between G2 and G30) and their dimerization partner HIF1β (2 fold between G2 and G30) in nuclear extracts while decreasing HIF1β levels in cytosolic extracts; the effect of G30 on HIFα protein levels was only half that induced of 100 µM CoCl2. Glucose stimulation also increased pimonidazole-adduct formation in islets, but to a lesser extent than culture under hypoxic conditions (17-fold in G30 vs G5, 99-fold in 5% vs 20% O2 in G5); after culture in G30, pimonidazole staining was heterogeneous between cells but was, on average, similar in the center and periphery of the islets. In vivo, the mRNA levels of several HIF target genes (Adm, Gapdh, Aldoa, Lactate dehydrogenase A, Enolase 1) were significantly increased (~2 to 3 fold) in islets from diabetic db/db vs non diabetic db/+ mice. Conclusion: High glucose induces moderate hypoxia in cultured rat β cells, thereby leading to HIF1α and HIF2α protein stabilization, HIF1/2α-HIF1β dimer translocation to the nucleus, and increased expression of glycolytic enzymes and other HIF target genes. These effects, which likely result from the glucose acceleration of mitochondrial metabolism and stimulation of O2 consumption, could contribute to in vitro β-cell glucotoxicity in whole islets and insulin-secreting cell lines. The up-regulation of HIF target genes in islets from db/db mice suggests that β-cell hypoxia also occurs in vivo in type 2 diabetes

    Structure génétique de la population porcine férale de Martinique

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    Structure génétique de la population porcine férale de Martinique. 51. Journées de la Recherche Porcin
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