42 results on '"Lautier C"'
Search Results
2. Follow-up study of two sisters with type A syndrome of severe insulin resistance gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy outcome: a case report
- Author
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Vambergue, A., Lautier, C., Valat, A.S., Cortet-Rudelli, C., Grigorescu, F., and Dewailly, D.
- Published
- 2006
3. Branched-Chain Amino Acid Database Integrated in MEDIPAD Software as a Tool for Nutritional Investigation of Mediterranean Populations
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Universitat Rovira i Virgili, Haydar S; Paillot T; Fagot C; Cogne Y; Fountas A; Tutuncu Y; Vintila M; Tsatsoulis A; Chi PT; Garandeau P; Chetea D; Badiu C; Gheorghiu M; Ylli D; Lautier C; Jarec M; Monnier L; Normand C; Šarac J; Barakat A; Missoni S; Pugeat M; Poucheret P; Hanzu F; Gomis R; Macias JM; Litvinov S; Khusnutdinova E; Poiana C; Pasquali R; Lauro D; Sesti G; Trischitta V; Abdelhak S; Zenati A; Ylli A; Satman I; Kanninen T; Rinato Y; Grigorescu F, Universitat Rovira i Virgili, and Haydar S; Paillot T; Fagot C; Cogne Y; Fountas A; Tutuncu Y; Vintila M; Tsatsoulis A; Chi PT; Garandeau P; Chetea D; Badiu C; Gheorghiu M; Ylli D; Lautier C; Jarec M; Monnier L; Normand C; Šarac J; Barakat A; Missoni S; Pugeat M; Poucheret P; Hanzu F; Gomis R; Macias JM; Litvinov S; Khusnutdinova E; Poiana C; Pasquali R; Lauro D; Sesti G; Trischitta V; Abdelhak S; Zenati A; Ylli A; Satman I; Kanninen T; Rinato Y; Grigorescu F
- Abstract
Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d'Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27⁻65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration.
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- 2018
4. HOW GENETICISTS CONTRIBUTE TO UNDERSTANDING OF COVID-19 DISEASE PATHOGENICITY.
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Grigorescu, F. and Lautier, C.
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COVID-19 , *COVID-19 pandemic , *MOLECULAR genetics , *POPULATION , *GENETICISTS - Abstract
Human populations are faced to the COVID-19 pandemic due to the emerging SARS-CoV-2 coronavirus originating from Wuhan (China) and with dramatic Public Health consequences. Despite periods of panic, the scientific community demonstrated an incredible innovation potential and energy ending up in one year with new vaccines to be used in population. Researchers are interrogating on how individual genetic differences contribute to the diversity of clinical manifestations or ethnic and geographic disparities of COVID-19. While efforts were spent to understand mechanistically the infectious potential of the virus, recent progresses in molecular genetics and bioinformatics allowed the characterization of viral sequence and construction of phylogeographical maps of viral dispersion worldwide. These data will help understanding epidemiological disparities among continents and ethnic populations. Much effort was also spent in analyzing host genetics by studying individual genes involved in innate and immune responses or explaining pathogenesis of comorbidities that complicate the fate of elderly patients. Several international consortia launched already Genome wide Association Studies (GWAS) and whole genome sequencing strategies to identify genetic markers with immediate application in patients at risk of respiratory failure. These new genetic data are important not only for understanding susceptibility factors for COVID-19 but they also contain an important message of hope for mankind warranting our survival and health. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
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5. L’amélioration du signal d’association du gène LHCGR au syndrome des ovaires polykystiques par une étude comparative de deux populations française et tunisienne
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Douma, Z., primary, Haydar, S., additional, Dallel, M., additional, Ben Salem, A., additional, Ben Lamine, L., additional, Sellami, N., additional, Hadi, J.C., additional, Hachani Ben Ali, F., additional, Lautier, C., additional, Pugeat, M., additional, Mahjoub, T., additional, and Grigorescu, F., additional
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- 2018
- Full Text
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6. Les gènes intervenant dans l’homéostasie du zinc sont impliqués dans les altérations cliniques et biologiques du syndrome des ovaires polykystiques
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Ilie, M.D., primary, Haydar, S., additional, Baculescu, N., additional, Vintila, M., additional, Gheorghiu, M., additional, Lautier, C., additional, Normand, C., additional, Poiana, C., additional, Badiu, C., additional, Pugeat, M., additional, and Grigorescu, F., additional
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- 2017
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7. PORTABILITY OF GWAS RESULTS BETWEEN ETHNIC POPULATIONS: GENETIC MARKERS FOR POLYCYSTIC OVARY SYNDROME (PCOS) IN MEDITERRANEAN AREA.
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Douma, Z., Lautier, C., Haydar, S., Mahjoub, T., and Grigorescu, F.
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POLYCYSTIC ovary syndrome , *GENETIC markers , *ANOVULATION , *LINKAGE disequilibrium , *GENE flow , *POPULATION genetics - Abstract
Genome Wide Association Studies (GWAS) are excellent opportunities to define culprit genes in complex disorders such as the polycystic ovary syndrome (PCOS). PCOS is a prevalent disorder characterized by anovulation, hyperandrogenism and polycystic ovaries, which benefitted from several GWASs in Asians and Europeans revealing more than 20 potential culprit genes near associated single nucleotide variations (SNV). Translation of these findings into the clinical practice raises difficulties since positive hits are surrogate SNVs linked with causative mutations by linkage disequilibrium (LD). Studies in Mediterranean populations (e.g. Southern Europe and North Africa) raise supplementary problems because of a different LD-pattern, which may disrupt the link with causative mutations. Our experience in MEDIGENE program between Tunisia and France enforces the necessity of genetic anthropology studies before translating GWAS data. Tunisians are a heterogeneous population with ancestral Berbers, European, Arab and Sub-Saharan African components while South Europeans display a high level of genetic diversity, partially explained by gene flow from North Africa. Human diversity studies require sampling from Middle East and North Africa (MENA) region that will help to understand genetic factors in complex diseases. [ABSTRACT FROM AUTHOR]
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- 2019
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8. BRANCHED CHAIN AMINO ACIDS AT THE EDGE BETWEEN MENDELIAN AND COMPLEX DISORDERS.
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Haydar, S., Lautier, C., and Grigorescu, F.
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BRANCHED chain amino acids , *METABOLOMICS , *BIOLOGICAL tags , *DISEASE progression , *INSULIN resistance , *NUTRITIONAL genomics - Abstract
Branched chained amino acids (BCAA) are essential components of the human diet and important nutrient signals, which regain particular interest in recent years with the avenue of metabolomics studies suggesting their potential role as biomarkers. There is now compelling evidence for predictive role of BCAA in progression of diabetes, but causality relationship is still debated concerning insulin resistance and genetic versus nongenetic pathogenesis. Mendelian randomization studies in large cohorts of diabetes indicated pathogenic role of PPM1K (protein phosphatase Mg2+/Mn2+ dependent 1K) on Chr 4q22.1 gene, encoding for a phosphatase that activate BCKDH (branched chain keto acid dehydrogenase) complex. Recent studies indicated that insulin rapidly and dose-dependently regulates gene expression of the same complex, but the relationship with systemic insulin resistance and glucose levels is complex. Rare genetic syndromes due to Mendelian mutations in key genes in BCAA catabolism may be good models to understand potential role of gene of BCAA catabolism. However, in studying complex disorders geneticists are faced to complete new aspects of metabolic regulation complicating understanding genetics of obesity, diabetes or metabolic syndrome. A review of genetic syndromes of BCAA metabolism suggests that insulin resistance is not present, except rare cases of methylmalonic aciduria due to MUT (methylmalonyl-coA mutase) gene on Chr 6p12.3. Another aspect that complicates understanding is the new role of central nervous system (CNS) in insulin resistance. For long time the hypothalamic hunger/satiety neuronal system was considered a key site of nutrient regulation. Genes may also affect the brain rewarding system (BRS) that would regulate food intake by modulating the motivation to obtain food and considering hedonic properties. Nutrigenomic and nutrigenetic investigations taking into account concurrently BCAA intake, metabolic regulation and gene variation have large perspectives to merge genetic and nutritional understanding in complex disorders. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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9. GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling
- Author
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Giovannone, B., primary, Tsiaras, W. G., additional, de la Monte, S., additional, Klysik, J., additional, Lautier, C., additional, Karashchuk, G., additional, Goldwurm, S., additional, and Smith, R. J., additional
- Published
- 2009
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10. Identification and sequence analysis of arginine vasopressin mRNA in normal and Brattleboro rat aortic tissue
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Mechaly, I, primary, Macari, F, additional, Lautier, C, additional, Serrano, JJ, additional, Cros, G, additional, and Grigorescu, F, additional
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- 1998
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11. Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.
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El Mkadem, Samira Ait, Lautier, Corinne, Macari, Francoise, Molinari, Nicolas, Lefebvre, Patrick, Renard, Eric, Gris, Jean Christophe, Cros, Gerard, Daures, Jean Pierre, Bringer, Jacques, White, Morris F., Grigorescu, Florin, El Mkadem, S A, Lautier, C, Macari, F, Molinari, N, Lefèbvre, P, Renard, E, Gris, J C, and Cros, G
- Subjects
ALLELES ,INSULIN ,OVARIAN cysts - Abstract
To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. [ABSTRACT FROM AUTHOR]
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- 2001
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12. 35th Annual Meeting of the European Association for the Study of Diabetes
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patanè, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., de Vos, P., Visser, L., de Haan, B. J., Klok, P., van Schilfgaarde, R., Poppema, S., Juang, J.-H., Kuo, C.-H., Hsu, B. R.-S., Nacher, V., Pérez, M., Biarnés, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Büsing, M., Becker, T., Klempnauer, J., Hücking, K., Schmiegel, W. H., Nauck, M. A., Bouček, P., Saudek, F., Adamec, M., Kožitarová, R., Jedináková, T., Vlasáková, Z., Skibová, J., Bartoš, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J.-C., Gillespie, J. S., McMaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Véricel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P.-O., MŞengül, A., Salman, F., Sargrn, M., Özer, E., Karşidaǧ, K., Salman, S., Gedik, S., Satman, İ., Dinççaǧ, N., Yılmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., van der Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., van der Ploeg, H. M., Danne, T., Hoey, H., McGee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hägglöf, B., Lugari, R., Dell’Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa., Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., García-Martínez, J. A., Villanueva-Peñacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahrén, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E.-J., Knospe, S., Glund, K., Demuth, H.-U., Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Goldstein, David S., Van Huysen, C., Stevens, M. 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- 1999
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13. Interaction between calpain 10 and IRS2 genes as determinants of glucose homeostasis in Caucasian and Amerindian populations
- Author
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Grigorescu, F., Serban Radian, Perez-Bravo, F., Lautier, C., Barros-Monteiro, J., and Brun, Jf
14. Complex haplotypes of IRS-2 gene are associated with obesity and reveal distinct effects on insulin secretion in obese and lean subjects
- Author
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Bringer, J., Jean-Christophe GRIS, Renard, E., Brun, Jf, Lautier, C., and Grigorescu, F.
15. 35th Annual Meeting of the European Association for the Study of Diabetes : Brussels, Belgium, 28 September-2 October 1999
- Author
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Ad Darts Memo, Morris For The Collaboration, Juhl, C., Porksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th, Muller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Bjorn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H-M, Oksanen, L., Tuomainen, T-P, Kontula, K., Salonen, J. T., Dekker, J. M., Boks, P., Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., Macalpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M. Jr, Kozakova, H., Kaas, A., Kofronova, O., Tlaskalova-Hogenova, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sorensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Hasko, G., Szabo, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H-H, Genediab, Study Group, Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabak, A. Gy, Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Canton, A., Burgos, R., Hernandez, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simo, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., Mcdermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. 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I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessieres-Lacombe, S., Gedec, Study Group, Tauber, J-P, Home, P. D., Lindholm, A., Riis, A., European Insulin Aspart Study Group, Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Us Dm, Study Group Of Insulin Glargine In Type, Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Hvidore Study group on Childhood Diabetes, Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Ukpds, Group, Steiner, G., Dais, Project Group, Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Verges, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph, Benko, B., Ljubic, S., Turk, Z., Granic, M., Marz, W., Wollschlager, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O Rahilly, S., Hattersley, A. T., Mccarthy, M. 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D., Schick, F., Diraison, F., Moulin, P., Beylot, M., Thams, P., Capito, K., Eliasson, Lena, Barg, Sebastian, Gopel, Sven, Kanno, Takahiro, Renstrom, Erik, Meda, P., Charollais, A., Gjnovci, A., Calabrese, A., Wonkam, A., Caton, D., Wisznievski, L., Serre, V., Cogne, F., Bauquis, J., Bosco, D., Huarte, J., Herrera, P., Gotfredsen, C. F., Vessby, B., Kanwu, Study Group, Manuel Y Keenoy, B., Engelen, W., Vertommen, J., Schrans, S., Louheranta, A., Lindstrom, J., Tuomilehto, J., Finnish Diabetes Prevention Study Group, Segal, K. R., Heymsfield, S., Hauptman, J., Boldrin, M., Lucas, C., Pandolfi, A., Cetrullo, D., Polishchuck, R., Alberta, M., Pellegrini, G., Calafiore, A., Vitacolonna, E., Capani, F., Consoli, A., Halleux, C. M., Gillot, E. F., Brichard, S. M., Planken, M., Corthouts, B., Peiffer, F., Scholten, D., Walke, M., Assert, R., Pirags, V., Pedula, K. L., Hillier, T. A., Brown, J. B., Eurodiab, Prospective Complications Study Group, Santini, S. A., Marra, G., Cotroneo, P., Manto, A., Di Leo, M. A. S., Di Gregorio, S., Tordi, A., Pitocco, D., Ruotolo, V., Ghirlanda, G., Temelkova-Kurktschiev, T., Schaper, F., Koehler, C., Henkel, E., Hanefeld, M., Mancini, L., Citterio, F., Cotroneo, A., Ceroone, S., Castagneto, M., Rajbhandari, S. M., Dent, M. T., Plater, M. E., Harris, N. D., Tesfaye, S., Ward, J. D., Dupuy, O., Mayaudon, H., Lecoules, S., Bauduceau, B., Palou, M., Farret, O., Molinie, C., Antonelli-Incalzi, R., Fuso, L., Giordano, A., Calcagni, M. L., Todaro, L., Basso, S., Tramaglino, L. M., Troncone, L., Pistelli, R., Guillot, R., Bringuier, A., Porokhov, B., Guillausseau, P. J., Feldmann, G., Zivanic, S., Cizmic, M., Dragojevic, R., Vanovic, M., Borghouts, L. B., Kranenburg, G. P. J., Schaart, G., Keizer, H. A., Niess, A. M., Dickuth, H. H., Lutz, O., Barbe, P., Calazel-Fournier, C., Hernandez, G., Saint-Martin, F., Galitzky, J., Goncalves, A. A., Da Silva, E. C., Brito, I. J. L., Da Silva, C. A., Lawrence, N. 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A., Marco, J., Khan, Akhtar, Ling, Zong-Chao, Ahren, Bo, Efendic, Suad, Bunting, C., Du, X., Zhi Sui, G., Rosen, P., Koschinsky, T., Kearney, T. M., Sharp, P. S., Lapolla, A., Fedele, D., Martano, L., Garbeglio, M., Seraglia, R., Favretto, D., Traldi, P., Meerwaldt, R., Smit, A. J., Links, Th P., V Roon, A. M., Graaf, R., Gans, R. O. B., Deyneli, O., Ersoz, H. O., Gogas, D., Fak, A. S., Akalin, S., Veglio, M., Sivieri, R., Chinaglia, A., Scaglione, L., Neuropathy Study Group of the Italian Society of the Study of Diabetes, Le, T., Wong, N., Detrano, R., Charles, M. A., Colhoun, H. M., Francis, D. P., Rubens, M., Underwood, S. R., Fuller, J. H., Knudsen, E., Sato, A., Nielsen, F. S., Bonora, E., Kiechl, S., Willeit, J., Oberhollenzer, F., Egger, G., Bonadonna, R., Muggeo, M., Festa, A., D Agostino, R. Jr, Howard, G., Mykkanen, L., Tracy, R. P., Haffner, S. M., Poulsen, P., Vach, K., European Group for the Study of Insulin Resistance (EGIR), Ijzerman, R. G., Bakker, S. J. 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W., Rosenbauer, J., Grabert, M., German Working Group on Quality Control, Icks, A., Schwab, O., Reile, K., German Pediat. Working Group, Janssen, M. M. J., Jongh, R. T., Casteleijn, S., Masurel, N., Hoogma, R. P. L. M., Santeusanio, F., Brunetti, P., Fanelli, C. G., Laureti, S., Bartocci, L., Maran, A., Crepaldi, C., Trupiani, S., Macdonald, I. A., Avogaro, A., Bouman, S. D., Keitz, M., Bruggink, J. E., Scheurink, A. J. W., Strubbe, J. H., Steffens, A. B., Ferguson, S. C., Mccrimmon, R. J., Perros, P., Best, J. J. K., Deary, I. J., Frier, B. M., Robinson, R. T. C. E., Ireland, N. H., Bedford, C., Fairclough, E., Hudson, S., Heller, S. R., Borch-Johnsen, K., Berger, M., Overmann, H., Bender, R., Blank, M., Sawicki, P., Jorgens, V., Muhlhauser, I., Nosadini, R., Sailer, A., Dalla Vestra, M., Brocco, E., Piarulli, F., Frigato, F., Sambataro, M., Velussi, M., Baggio, B., Fioretto, P., Jager, A., Hinsbergh, V. W. M., Kostense, P. 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F., Motala, A. A., Omar, M. A. K., Tzaneva, V., Iotova, V., Jaeger, C., Hatziagelaki, E., Stroedter, A., Becker, F., Bretzel, R. G., Strebelow, M., Schlosser, M., Ziegler, B., Ziegler, M., Wassmuth, R., Ostrauskas, R., Zalinkevicius, R., Norkus, A., Lithuanian Collaborative Group for the Epidemiology of Diabetes, Jarosz-Chobot, P., Otto-Buczkowska, E., Koehler, B., Maklakiewicz, E., Green, A., Ionescu-Tirgoviste, C., Serban, V., Guja, C., Mota, M., Creteanu, G., Calin, A., Morosanu, M., Ferariu, I., Halmagy, I., Cristescu, I., Strugariu, M., Minescu, A., Barbul, R., Visalli, N., Sabastiani, L., Adorisio, E., Cassone Faldetta, M. R., Multari, G., Casu, A., Songini, M., Pozzilli, P., Imdiab, Study Group, Muntoni, Sa, Waananen, S., Law, G., Muntoni, S., Shubnikov, E., Choubnikova, J., Mikulecky, M., Michalkova, D., Hlava, P., Teuscher, A. U., Reinli, K., Teuscher, A., Zhao, H. X., Stenhouse, E., Moyeed, R., Demaine, A. G., Millward, B. A., Feltbower, R. G., Holland, P., Campbell, F., Fear, N. T., Wasmuth, H. E., Elliott, R. B., Mclachlan, C., Erhardt, G., Kolb, H., Guaita, G., Pelligra, I., Motzo, C., Obinu, M., Cossu, E., Cirillo, R., Kinalski, M., Kretowski, A., Bingley, P., Kinalska, I., Douek, I. F., Bingley, P. J., Gale, E. A. M., Imagawa, A., Hanafusa, T., Miyagawa, J., Matsuzawa, Y., Iddm, Osaka Study Group, Todd, J. A., Welsh, K., Marshall, S., Nolsoe, R., Kristiansen, O. P., Larsen, Z., Johannesen, J., Jahromi, M. M., Larsen, Z. M., Kyvik, K. O., Jeanclos, E., Schork, N. J., Aviv, A., Sieradzki, J., Malecki, M. T., Klupa, T., Hanna, L., Sieradzka, J., Frey, J., Krolewski, A. S., Calvo, B., Bilbao, J. R., Perez Nanclares, G., Castano, L., Santos, J. L., Perez-Bravo, F., Piquer, S., Puig-Domingo, M., Carrasco, E., Calvillan, M., Leiva, A., Albala, C., Cavallo, M. G., Manca Bitti, M. L., Suraci, C., Crino, A., Giordano, C., Cervoni, M., Sbriglia, M. 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16. Dense genetic mapping of IGF-1 receptor gene indicates genetic association of complex haplotypes with fetal death
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Lautier, C., Smith, R. J., Gris, J. C., and Florin Grigorescu
17. Interethnic diversity of SNP and haplotypes of IRS-2 gene explains variability in insulin resistance associated with PCO syndrome
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Grigorescu, F., Lautier, C., Lefebvre, P., Fica, S., Serban Radian, Coculescu, M., and Bringer, J.
18. Molecular genetics strategies to identify vasotocin coding sequences in humans: Family-specific approach using genomic DNA and fetal tissues mRNAs
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Radian, S., Bensaada, M., Lautier, C., Jean-Pierre Molès, Grigorescu, F., Gussi, I., Badiu, C., Nastasia, S., Hudita, D., Leonte, L., Marinescu, B., and Coculescu, M.
19. L’amélioration du signal d’association du gène LHCGRau syndrome des ovaires polykystiques par une étude comparative de deux populations française et tunisienne
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Douma, Z., Haydar, S., Dallel, M., Ben Salem, A., Ben Lamine, L., Sellami, N., Hadi, J.C., Hachani Ben Ali, F., Lautier, C., Pugeat, M., Mahjoub, T., and Grigorescu, F.
- Abstract
Afin d’améliorer le diagnostic dans le syndrome des ovaires polykystiques (SOPK), nous avons exploré l’association du gène LHCGR(luteinizing hormone/choriogonadotropin receptor) avec ce syndrome dans la population française FR (n=526 dont 235 SOPK) et tunisienne TN (n=96 dont 61 SOPK). Cette étude était suivie par une réplication de 4 marqueurs de GWAS antérieurs sur la population TN (n=629).
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- 2018
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20. INSULIN RESISTANCE AND PATHOGENESIS OF POSTMENOPAUSAL OSTEOPOROSIS.
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Greere, D. I. I., Grigorescu, F., Manda, D., Lautier, C., and Poianã, C.
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OSTEOPOROSIS in women , *INSULIN resistance , *BONE density , *BODY composition , *INSULIN receptors , *BONE fractures - Abstract
Osteoporosis (OP) is a disease predisposing postmenopausal women to fractures, and often accompanied by insulin resistance (IR) and metabolic syndrome (MetS). Previous studies provided contradictory results concerning prevalence of MetS in postmenopausal OP. To better understand the pathogenesis of IR, we reviewed cellular and molecular aspects and systematically reviewed studies providing homeostasis model assessment (HOMA) index. Bone is an active endocrine organ maintaining its integrity by orchestrated balance between bone formation and resorption. Both osteoblasts and osteoclasts contain receptors for insulin and insulin-like growth factor-1 (IGF-1) operating in skeletal development and in the adult life. Defects in this system generate systemic IR and bone-specific IR, which in turn regulates glucose homeostasis and energy metabolism through osteocalcin. Examination of genetic syndromes of extreme IR revealed intriguing features namely high bone mineral density (BMD) or accelerated growth. Studies of moderate forms of IR in postmenopausal women reveal positive correlations between HOMA index and BMD while correlations with osteocalcin were rather negative. The relation with obesity remains complex involving regulatory factors such as leptin and adiponectin to which the contribution of potential genetic factors and in particular, the correlation with the degree of obesity or body composition should be added. [ABSTRACT FROM AUTHOR]
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- 2023
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21. IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.
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Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, Kiess W, Klammt J, Kratzsch J, Osgood D, Pfäffle R, Raile K, Seidel B, Smith RJ, Chernausek SD, and Intrauterine Growth Retardation (IUGR) Study Group
- Published
- 2003
22. Les traités médiévaux sur le vitrail
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Boulanger, Karine, Centre André Chastel : Laboratoire de recherche sur le patrimoine français et l'histoire de l'art occidental (CACLRPFHAO), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris-Sorbonne (UP4), Lautier C. et Sandron D., and Boulanger, Karine
- Subjects
Moyen Age ,traités techniques ,[SHS.ART] Humanities and Social Sciences/Art and art history ,[SHS.ART]Humanities and Social Sciences/Art and art history ,vitrail - Abstract
étude des traités médiévaux consacrés à la technique du vitrail : traités de Théophile, d'Antoine de Pise, de Formica, du moine de l'abbaye de Zagan et du Kunstbuch
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- 2008
23. La peinture sur verre à Florence au temps d'Antoine de Pise
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Boulanger, Karine, Lautier, Claudine, Centre André Chastel : Laboratoire de recherche sur le patrimoine français et l'histoire de l'art occidental (CACLRPFHAO), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris-Sorbonne (UP4), Boulanger, Karine, Lautier C. et Sandron D., and Lautier, Claudine
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XIVe siècle ,Antoine de Pise ,Moyen Age ,Agnolo Gaddi ,Santa Maria Novella ,Orsanmichele ,peinture murale ,[SHS.ART] Humanities and Social Sciences/Art and art history ,Florence ,XVe siècle ,Santa Croce ,[SHS.ART]Humanities and Social Sciences/Art and art history ,vitrail - Abstract
étude des grands chantiers de peinture sur verre à Florence à la fin du 14e siècle
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- 2008
24. Le vitrail d'Antoine de Pise
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Boulanger, Karine, Centre André Chastel : Laboratoire de recherche sur le patrimoine français et l'histoire de l'art occidental (CACLRPFHAO), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université Paris-Sorbonne (UP4), Lautier C. et Sandron D., and Boulanger, Karine
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Moyen Age ,Antoine de Pise ,[SHS.ART] Humanities and Social Sciences/Art and art history ,Florence ,[SHS.ART]Humanities and Social Sciences/Art and art history ,vitrail - Abstract
étude du vitrail réalisé par Antoine de Pise à la cathédrale de Florence en 1396
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- 2008
25. Fine-Scale Haplotype Mapping Reveals an Association of the FTO Gene with Osteoporosis and Fracture Risk in Postmenopausal Women.
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Greere D, Haydar S, Grigorescu F, Manda D, Voicu G, Lautier C, and Poiana C
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- Humans, Female, Middle Aged, Aged, Fractures, Bone genetics, Postmenopause genetics, Genetic Predisposition to Disease, Low Density Lipoprotein Receptor-Related Protein-5 genetics, Osteoporosis, Postmenopausal genetics, Bone Density genetics, Osteoporotic Fractures genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Haplotypes, Polymorphism, Single Nucleotide
- Abstract
Introduction: The Fat Mass and Obesity-Associated ( FTO ) gene encodes a demethylase, which modulates RNA N6-methyladenosine (m6A) and plays a regulatory role in adipocyte differentiation and the pathogenesis of human obesity., Methods: To understand the potential role of FTO in osteoporosis (OP), we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, and rs9930506) of the FTO gene, and a missense SNV i.e., rs3736228 (A1330V), located in exon 18 of the LRP5 gene, in a cohort of postmenopausal women ( n = 188) from Central Europe. Genotyping was performed with an allele discrimination assay, while haplotypes were reconstructed in the population by PHASE 2.1., Results: The rs9930506 was strongly associated with OP ( p < 0.0035), which was supported by Bonferroni correction ( p < 0.0175), and all SNVs located in the FTO gene were more strongly associated with severe OP with fragility fractures. Among seventeen haplotypes detected for the FTO gene, two haplotypes (H1 and H9) were frequent (frequency > 10%) and distributed in three main haplotypes pairs (H1/H1, H1/H9 and H9/H9, respectively). The pathogenic pair H1/H9 was associated with a leaner phenotype, increased fracture risk, and a lower bone mineral density (BMD), and carried the heterozygous GA of rs9930506, while the protective pair H9/H9 was associated with an increased obesity risk and carried AA alleles of rs9939609., Conclusions: Concordant associations with OP, an increased fracture risk, and a lower BMD at all skeletal sites indicate that the FTO gene is a promising candidate for OP, explaining the complex relationship with obesity and offering new perspectives for the study of the epigenetic regulation of bone metabolism.
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- 2024
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26. Relative Contribution of Metabolic Syndrome Components in Relation to Obesity and Insulin Resistance in Postmenopausal Osteoporosis.
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Greere D, Grigorescu F, Manda D, Voicu G, Lautier C, Nitu I, and Poiana C
- Abstract
Introduction . Osteoporosis (OP) affects 30% of postmenopausal women, often complicated by metabolic syndrome (MetS) with a still controversial role. We aimed to characterize MetS and its components in relation to bone mineral density (BMD), body mass index (BMI), and insulin resistance. Methods . Patients ( n = 188) underwent DEXA scans, spine X-rays, and metabolic and hormonal investigations, including bone biomarkers, muscular strength, and physical performance tests, while insulin resistance was evaluated by the Homeostasis Model Assessment (HOMA-IR). Results . Patients with a normal BMD or osteopenia ( n = 68) and with OP ( n = 120) displayed 51.5% and 30.8% of MetS, but without differences in insulin resistance. When BMD was studied as a function of the cumulative MetS criteria and centiles of BMI, lower levels of BMD were observed beyond an inflection point of 27.2 kg/m
2 for BMI, allowing for further stratification as lean and overweight/obese (OW/OB) subjects. In contrast with lean individuals ( n = 74), in OW/OB patients ( n = 46), MetS was associated with HbA1c ( p < 0.0037, OR 9.6, 95% CI [1.64-55.6]) and insulin resistance ( p < 0.0076, OR 6.7, 95% CI [1.49-30.8]) in the context where BMD values were lower than those predicted from BMI in non-OP subjects. In OP patients with fragility fractures (31% of MetS), glycemia also appeared to be the dominant factor for MetS ( p < 0.0005, OR 4.1, 95% CI [1.63-10.39]). Conclusions . These data indicate a detrimental effect of insulin resistance in MetS on OP patients, while the prevalence of the syndrome depends on the proportion of obesity. These findings provide new insights into the pathogenic role of MetS and reveal the need to consider different strata of BMI and insulin resistance when studying postmenopausal OP.- Published
- 2024
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27. Characterization of sinoatrial automaticity in Microcebus murinus to study the effect of aging on cardiac activity and the correlation with longevity.
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DiFrancesco ML, Marrot M, Torre E, Mesirca P, Davaze R, Lautier C, Fontes P, Cuoq J, Fernandez A, Lamb N, Pifferi F, Mestre-Francés N, Mangoni ME, and Torrente AG
- Subjects
- Humans, Rats, Animals, Longevity, Aging physiology, Heart, Heart Rate physiology, Mammals, Cheirogaleidae
- Abstract
Microcebus murinus, or gray mouse lemur (GML), is one of the smallest primates known, with a size in between mice and rats. The small size, genetic proximity to humans and prolonged senescence, make this lemur an emerging model for neurodegenerative diseases. For the same reasons, it could help understand how aging affects cardiac activity. Here, we provide the first characterization of sinoatrial (SAN) pacemaker activity and of the effect of aging on GML heart rate (HR). According to GML size, its heartbeat and intrinsic pacemaker frequencies lie in between those of mice and rats. To sustain this fast automaticity the GML SAN expresses funny and Ca
2+ currents (If , ICa,L and ICa,T ) at densities similar to that of small rodents. SAN automaticity was also responsive to β-adrenergic and cholinergic pharmacological stimulation, showing a consequent shift in the localization of the origin of pacemaker activity. We found that aging causes decrease of basal HR and atrial remodeling in GML. We also estimated that, over 12 years of a lifetime, GML generates about 3 billion heartbeats, thus, as many as humans and three times more than rodents of equivalent size. In addition, we estimated that the high number of heartbeats per lifetime is a characteristic that distinguishes primates from rodents or other eutherian mammals, independently from body size. Thus, cardiac endurance could contribute to the exceptional longevity of GML and other primates, suggesting that GML's heart sustains a workload comparable to that of humans in a lifetime. In conclusion, despite the fast HR, GML replicates some of the cardiac deficiencies reported in old people, providing a suitable model to study heart rhythm impairment in aging. Moreover, we estimated that, along with humans and other primates, GML presents a remarkable cardiac longevity, enabling longer life span than other mammals of equivalent size., (© 2023. The Author(s).)- Published
- 2023
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28. Sex-specific patterns of age-related cerebral atrophy in a nonhuman primate Microcebus murinus.
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Fritz RG, Zimmermann E, Picq JL, Lautier C, Meier M, Kästner S, and Schmidtke D
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- Animals, Atrophy, Brain diagnostic imaging, Female, Magnetic Resonance Imaging, Male, Aging pathology, Brain pathology, Cheirogaleidae, Sex Characteristics
- Abstract
Steadily aging populations result in a growing need for research regarding age-related brain alterations and neurodegenerative pathologies. By allowing a good translation of results to humans, nonhuman primates, such as the gray mouse lemur Microcebus murinus, have gained attention in this field. Our aim was to examine correlations between atrophy-induced brain alterations and age, with special focus on sex differences in mouse lemurs. For cerebral volumetric measurements, in vivo magnetic resonance imaging was performed on 59 animals (28♀♀/31♂♂) aged between 1.0 to 11.9 years. Volumes of different brain regions, cortical thicknesses, and ventricular expansions were evaluated. Analyses revealed significant brain atrophies with increasing age, particularly around the caudate nucleus, the thalamus, and frontal, parietal, and temporo-occipital regions. Especially old females showed a strong decline in cingulate cortex thickness and had higher values of ventricular expansion, whereas cortical thickness of the splenium and occipital regions decreased mainly in males. Our study, thus, provides first evidence for sex-specific, age-related brain alterations in a nonhuman primate, suggesting that mouse lemurs can help elucidating the mechanism underlying sex disparities in cerebral aging, for which there is mixed evidence in humans., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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29. Association of estrogen receptor gene variants (ESR1 and ESR2) with polycystic ovary syndrome in Tunisia.
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Douma Z, Dallel M, Bahia W, Ben Salem A, Hachani Ben Ali F, Almawi WY, Lautier C, Haydar S, Grigorescu F, and Mahjoub T
- Subjects
- Adult, Estrogens genetics, Estrogens metabolism, Female, Genetic Association Studies, Genotype, Humans, Infertility, Female genetics, Infertility, Female pathology, Logistic Models, Middle Aged, Polycystic Ovary Syndrome pathology, Polymorphism, Restriction Fragment Length genetics, Polymorphism, Single Nucleotide genetics, Tunisia, Estrogen Receptor alpha genetics, Estrogen Receptor beta genetics, Genetic Predisposition to Disease, Polycystic Ovary Syndrome genetics
- Abstract
SNV (single nucleotide variation) in estrogen receptor (ESR1 and ESR2) genes are susceptibility markers for complex diseases, such as cancer, metabolic disorders and women infertility. We explored six widely used SNVs in ESR1 (rs2234693, rs9340799, rs3798577, rs3020314) and ESR2 (rs1256049, rs4986938) in polycystic ovary syndrome (PCOS) in women from Tunisia (n = 254) compared to controls (n = 170). Genotyping was performed by RFLP-PCR or real-time PCR and analyzed in GoldenHelix statistical package. Logistic regression revealed association of rs2234693, rs3798577 and rs3020314 (ESR1) and rs1256049 (ESR2), the association of rs2234693 (C/T) being the strongest with P < 4.81 × 10
-6 , 2.88 × 10-5 after Bonferroni correction, OR 0.31, 95%CI (0.18-0.53)). Correlations were found with LH, LH/FSH or hyperandrogenism and even more significant with metabolic syndrome (rs9340799) and hyperglycemia (rs3798577). Among 14 haplotypes reconstructed in ESR1gene, four haplotypes (H1 to H4) were associated with PCOS the strongest being that of H1 (P < 0.002) supported by Bonferroni (P < 0.033) and permutation tests (P < 4 x10-4 ). In haplotype trend regression, concordant correlations were found with insulin resistance (P < 0.033) for H2 and with high blood pressure for H3 (P < 0.048). While these data revealed influential role on metabolic rather and hormonal features of PCOS, the association of rs2234693 was the strongest among all ethnic populations studied thus far giving a new insight on estrogen receptor gene variation in distant North African populations and their role in metabolic alteration of PCOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)- Published
- 2020
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30. Fine-scale haplotype mapping of MUT, AACS, SLC6A15 and PRKCA genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation.
- Author
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Haydar S, Grigorescu F, Vintilă M, Cogne Y, Lautier C, Tutuncu Y, Brun JF, Robine JM, Pugeat M, Normand C, Poucheret P, Gheorghiu ML, Georgescu C, Badiu C, Băculescu N, Renard E, Ylli D, Badiou S, Sutra T, Cristol JP, Mercier J, Gomis R, Macias JM, Litvinov S, Khusnutdinova E, Poiana C, Pasquali R, Lauro D, Sesti G, Prudente S, Trischitta V, Tsatsoulis A, Abdelhak S, Barakat A, Zenati A, Ylli A, Satman I, Kanninen T, Rinato Y, and Missoni S
- Subjects
- Adult, Amino Acids, Branched-Chain metabolism, Female, Humans, Male, Metabolic Syndrome blood, Middle Aged, Amino Acid Transport Systems, Neutral genetics, Amino Acids, Branched-Chain genetics, Haplotypes, Insulin Resistance genetics, Metabolic Syndrome genetics, Nerve Tissue Proteins genetics, Polymorphism, Single Nucleotide, Protein Kinase C-alpha genetics
- Abstract
Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development of diabetes. To define determinants of insulin resistance (IR) we investigated 73 genes involved in BCAA metabolism or regulation by fine-scale haplotype mapping in two European populations with metabolic syndrome. French and Romanians (n = 465) were genotyped for SNPs (Affymetrix) and enriched by imputation (BEAGLE 4.1) at 1000 genome project density. Initial association hits detected by sliding window were refined (HAPLOVIEW 3.1 and PHASE 2.1) and correlated to homeostasis model assessment (HOMAIR) index, in vivo insulin sensitivity (SI) and BCAA plasma levels (ANOVA). Four genomic regions were associated with IR located downstream of MUT, AACS, SLC6A15 and PRKCA genes (P between 9.3 and 3.7 x 10-5). Inferred haplotypes up to 13 SNPs length were associated with IR (e.g. MUT gene with P < 4.9 x 10-5; Bonferroni 1.3 x 10-3) and synergistic to HOMAIR. SNPs in the same regions were also associated with one order of magnitude lower P values (e.g. rs20167284 in the MUT gene with P < 1.27 x 10-4) and replicated in Mediterranean samples (n = 832). In French, influential haplotypes (OR > 2.0) were correlated with in vivo insulin sensitivity (1/SI) except for SLC6A15 gene. Association of these genes with BCAA levels was variable, but influential haplotypes confirmed implication of MUT from BCAA metabolism as well as a role of regulatory genes (AACS and PRKCA) and suggested potential changes in transcriptional activity. These data drive attention towards new regulatory regions involved in IR in relation with BCAA and show the ability of haplotypes in phased DNA to detect signals complimentary to SNPs, which may be useful in designing genetic markers for clinical applications in ethnic populations., Competing Interests: The authors have declared that no competing interests exist. We confirm that commercial affiliation of BC Platforms Ltd Oy, Espoo, Finland and Intactile Design SA, Montpellier, France does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
- Full Text
- View/download PDF
31. Branched-Chain Amino Acid Database Integrated in MEDIPAD Software as a Tool for Nutritional Investigation of Mediterranean Populations.
- Author
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Haydar S, Paillot T, Fagot C, Cogne Y, Fountas A, Tutuncu Y, Vintila M, Tsatsoulis A, Thanh Chi P, Garandeau P, Chetea D, Badiu C, Gheorghiu M, Ylli D, Lautier C, Jarec M, Monnier L, Normand C, Šarac J, Barakat A, Missoni S, Pugeat M, Poucheret P, Hanzu F, Gomis R, Macias JM, Litvinov S, Khusnutdinova E, Poiana C, Pasquali R, Lauro D, Sesti G, Trischitta V, Abdelhak S, Zenati A, Ylli A, Satman I, Kanninen T, Rinato Y, and Grigorescu F
- Subjects
- Adult, Aged, Female, France, Greece, Humans, Male, Mediterranean Region, Middle Aged, Nutrition Surveys, Amino Acids, Branched-Chain analysis, Databases, Factual statistics & numerical data, Food Analysis methods, Nutrition Assessment, Software
- Abstract
Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d'Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27⁻65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
- Full Text
- View/download PDF
32. Diversity of Y-chromosomal and mtDNA Markers Included in Mediscope Chip within Two Albanian Subpopulations from Croatia and Kosovo: Preliminary Data.
- Author
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Čoklo M, Auguštin DH, Šarac J, Novokmet N, SIndik, Lewis, Petranovic, Mulahasanović LK, Khusnutdinova E, Litvinov S, Haydar S, Lautier C, Normand C, Attaoua R, Vintila M, Bosch-Comas A, Suarez, Jares P, Gomis R, Missoni S, Marjanović D, and Grigorescu F
- Subjects
- Chromosomes, Human, Y genetics, Croatia, DNA, Mitochondrial genetics, Female, Genetic Markers genetics, Humans, Kosovo, Male, Pilot Projects, White People genetics, Genetic Variation genetics, Genetics, Population methods, Oligonucleotide Array Sequence Analysis methods
- Abstract
The aim of this preliminary study is to analyze genetic specificity of Kosovo Albanians comparing with neighboring populations using new genetic tool - MEDISCOPE gene chip, to investigate the feasibility of this approach. We collected 37 DNA samples (9 Croats, 17 Albanians from Croatia and 11 Albanians from Kosovo) from unrelated males born in Croatia and Kosovo. Additionally, samples were expanded with female individuals and mtDNA analysis included a total of 61 samples (15 Croats, 23 Albanians from Croatia and 23 Albanians from Kosovo). This pilot study suggests that the usage of the MEDISCOPE chip could be recognized as an efficient tool within recognition of the population genetic specificity even within extremely small sample size.
- Published
- 2016
33. Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases.
- Author
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Verdier JM, Acquatella I, Lautier C, Devau G, Trouche S, Lasbleiz C, and Mestre-Francés N
- Abstract
Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer's and prion diseases) or motor deficits (Parkinson's and related diseases).
- Published
- 2015
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34. [Glucose homeostasis, diabetes and neurodegenerative disorders].
- Author
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Lautier C and Grigorescu F
- Subjects
- Cell Division, Cell Survival, Diabetes Complications metabolism, Disease Susceptibility, Humans, Insulin physiology, Insulin Resistance, Insulysin physiology, Nerve Tissue Proteins physiology, Neurodegenerative Diseases metabolism, Neurons pathology, Signal Transduction physiology, Somatomedins physiology, Diabetes Complications etiology, Glucose metabolism, Homeostasis, Neurodegenerative Diseases etiology
- Published
- 2009
- Full Text
- View/download PDF
35. Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease.
- Author
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Lautier C, Goldwurm S, Dürr A, Giovannone B, Tsiaras WG, Pezzoli G, Brice A, and Smith RJ
- Subjects
- Adult, Aged, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Pedigree, Carrier Proteins genetics, Chromosomes, Human, Pair 2 genetics, Mutation, Parkinson Disease genetics
- Abstract
The genetic basis for association of the PARK11 region of chromosome 2 with familial Parkinson disease (PD) is unknown. This study examined the GIGYF2 (Grb10-Interacting GYF Protein-2) (TNRC15) gene, which contains the PARK11 microsatellite marker with the highest linkage score (D2S206, LOD 5.14). The 27 coding exons of the GIGYF2 gene were sequenced in 123 Italian and 126 French patients with familial PD, plus 131 Italian and 96 French controls. A total of seven different GIGYF2 missense mutations resulting in single amino acid substitutions were present in 12 unrelated PD index patients (4.8%) and not in controls. Three amino acid insertions or deletions were found in four other index patients and absent in controls. Specific exon sequencing showed that these ten sequence changes were absent from a further 91 controls. In four families with amino acid substitutions in which at least one other PD case was available, the GIGYF2 mutations (Asn56Ser, Thr112Ala, and Asp606Glu) segregated with PD. There were, however, two unaffected carriers in one family, suggesting age-dependent or incomplete penetrance. One index case (PD onset age 33) inherited a GIGYF2 mutation (Ile278Val) from her affected father (PD onset age 66) and a previously described PD-linked mutation in the LRRK2 gene (Ile1371Val) from her affected mother (PD onset age 61). The earlier onset and severe clinical course in the index patient suggest additive effects of the GIGYF2 and LRRK2 mutations. These data strongly support GIGYF2 as a PARK11 gene with a causal role in familial PD.
- Published
- 2008
- Full Text
- View/download PDF
36. Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation.
- Author
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Lautier C, El Mkadem SA, Renard E, Brun JF, Gris JC, Bringer J, and Grigorescu F
- Subjects
- Adult, Alleles, Blood Glucose, Body Mass Index, Case-Control Studies, Female, Genotype, Glucose Tolerance Test, Haplotypes, Humans, Insulin Receptor Substrate Proteins, Intracellular Signaling Peptides and Proteins, Phenotype, Polymerase Chain Reaction, Receptor, Insulin genetics, Genetic Variation genetics, Glucose Intolerance genetics, Insulin Resistance genetics, Obesity genetics, Phosphoproteins genetics, Point Mutation, Polymorphism, Single Nucleotide genetics
- Abstract
In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome region: 13q34) in obesity, a complex disorder associated with insulin resistance and glucose intolerance, we determined single nucleotide polymorphims (SNPs) and complex haplotypes in women with morbid obesity and a body mass index (BMI) of 41+/-0.8 kg/m2 ( n=99) compared with controls having a BMI of 23.8+/-0.1 kg/m2 ( n=92). Sequencing of unphased DNA or digestion of polymerase chain reaction fragments revealed seven SNPs, including a new C/T(-769) replacement at the 5' untranslated region. Considering four or seven SNPs, we reconstructed with the PHASE program nine or 24 haplotypes, respectively, that were well correlated into the cladogram. Logistic regression analysis with nine haplotypes in the whole sample revealed that obesity was associated with haplotype H3, with P<0.025, an odds ratio (OR) of 1.9 and a 95% confidence interval (CI) of 1.1-3.4, or pairs 3/3 ( P<0.005, OR=8.7, CI=1.9-40.1) and 3/4 ( P<0.023, OR=2.5, CI=1.1-5.6), all containing the the Gly1057Asp allelic variant of IRS2, whereas controls were associated with H5 and H6 ( P<0.02, OR=0.2, CI=0.01-0.81). Although obese H5 carriers (also containing Gly1057Asp mutation) were the most insulin resistant, haplotypes of IRS2 were poorly correlated (analysis of variance) with insulin resistance. By contrast, haplotypes H3, H4 and pairs 3/3 were consistently associated with increased 2-h glucose levels during an oral glucose tolerance test in obese individuals ( P<0.0005, 0.025 and 0.027, respectively). These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.
- Published
- 2003
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37. Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus.
- Author
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Rasmussen SK, Lautier C, Hansen L, Echwald SM, Hansen T, Ekstrøm CT, Urhammer SA, Borch-Johnsen K, Grigorescu F, Smith RJ, and Pedersen O
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, Birth Weight, Codon, DNA Mutational Analysis, Denmark, Female, Gene Frequency, Humans, Insulin blood, Insulin pharmacology, Male, Middle Aged, Polymorphism, Genetic, Diabetes Mellitus, Type 2 genetics, Insulin-Like Growth Factor I genetics, Mutation, Receptor, IGF Type 1 genetics
- Abstract
Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. The impact of the most prevalent polymorphism, GAG1013GAA of the IGF-IR, was evaluated in a population-based sample of 349 young healthy subjects, where the variant had an allele frequency of 0.44 (95% confidence interval, 0.40-0.48). No significant relationships between this variant and birth weight, birth length, or insulin sensitivity index were detected. In addition, we did not observe any significant differences in allelic frequencies of the codon 1013 variant between 395 type 2 diabetic patients (allele frequency, 0.52; 95% confidence interval, 0.49-0.55) and 238 matched glucose-tolerant control subjects (allelic frequency, 0.47; 95% confidence interval, 0.43-0.50). In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population.
- Published
- 2000
- Full Text
- View/download PDF
38. Identification by RT-PCR and immunolocalization of arginine vasopressin in rat pancreas.
- Author
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Méchaly I, Macari F, Laliberté MF, Lautier C, Serrano JJ, Cros G, and Grigorescu F
- Subjects
- Animals, Immunohistochemistry, Male, Pancreas cytology, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction methods, Arginine Vasopressin analysis, Arginine Vasopressin genetics, Pancreas metabolism, Transcription, Genetic
- Abstract
Arginine vasopressin (AVP), a hormone of the hypothalamic pituitary axis, has been described in several peripheral tissues, including pancreas. To demonstrate the ectopic synthesis of AVP at the pancreatic level, we explored the expression of the AVP-neurophysin-II (AVP-NP-II) precursor gene by reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing and attempted to localise the peptide by immunocytochemistry in normal rat pancreas. Primers designed at the 3' and 5' ends of the AVP-NP-II gene, RT-PCR, and automatic sequencing of PCR products from rat pancreas revealed transcripts of the predicted size with an identical sequence to those from the hypothalamus. In addition, AVP antiserum revealed immunoreactive material of perivascular localisation. These data provide the first direct evidence for the presence of AVP transcripts in rat pancreatic tissue, whereas concurrent immunodetection of this hormone offers further support for the potential role of ectopic AVP in local regulation of the secretory activity of the pancreas.
- Published
- 1999
39. [Insulin resistance: from clinical diagnosis to molecular genetics. Implications in diabetes mellitus].
- Author
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Jaffiol C, Rouard M, Macari F, Lautier C, Ait el Mkadem S, Méchaly I, Brun JF, Renard E, Cros G, Bringer J, and Grigorescu F
- Subjects
- Acanthosis Nigricans genetics, Amino Acid Substitution, Animals, Epistasis, Genetic, Female, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance physiology, Models, Genetic, Phosphoproteins genetics, Phosphoproteins metabolism, Point Mutation, Polycystic Ovary Syndrome genetics, Receptor, Insulin metabolism, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Insulin Resistance genetics, Receptor, Insulin genetics
- Abstract
Insulin resistance is observed in several diseases such as non insulin dependent diabetes mellitus (NIDDM) or polycystic ovarian syndrome (PCOS). To understand genetic determinism of this abnormality we have developed a multidisciplinary approach including selection of phenotypes with insulin resistance confirmed in vivo by minimal model of Bergman and characterization of cellular defects in insulin action on circulating erythrocytes and monocytes. Exploration of variability in candidate genes by direct sequencing in some genetic syndromes of severe insulin resistance and acanthosis nigricans (mainly the Type A syndrome) revealed mutations of the insulin receptor gene associated with major defects in insulin binding or kinase activity. In other rare genetic syndromes or patients affected by NIDDM or PCOS defects appear to be located at post-receptor level, where IRS (insulin receptor substrate) genes are the most attractive candidates. Prevalence of some allelic variants suggested a potential role of IRS genes in insulin resistance, although their involvement in the pathogenesis of NIDDM remains controversial. Genotype-phenotype correlations in first degree relatives of an index case caring the Type A syndrome, suggested that association of allelic variants of IRS-1 and IRS-2 with insulin receptor mutations contribute, by synergistic effects, to phenotypic expression of defects in signal transduction. These mechanisms through genetic epistasis, involving several genes in insulin action, fit better with the polygenic nature of current forms of NIDDM and represent a good model in the study of pathogenesis of insulin resistance.
- Published
- 1999
40. Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family.
- Author
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Macari F, Lautier C, Girardet A, Dadoun F, Darmon P, Dutour A, Renard E, Bouvagnet P, Claustres M, Oliver C, and Grigorescu F
- Subjects
- Acanthosis Nigricans genetics, Africa, Northern ethnology, Chromosome Mapping, Consanguinity, Female, France epidemiology, Genetic Linkage, Genotype, Humans, Insulin Resistance genetics, Male, Pedigree, Syndrome, Abnormalities, Multiple genetics, Chromosomes, Human, Pair 2, Diabetes Mellitus, Type 2 genetics, Hearing Loss, Sensorineural genetics, Retinal Degeneration genetics
- Abstract
Alström syndrome is a rare autosomal recessive disorder characterized by retinal pigment degeneration, neurogenic deafness, infantile obesity, hyperlipidemia, and non-insulin-dependent diabetes mellitus. While the disease-related gene remains unknown, studies of the genetic isolate of French Acadians provisionally locate the Alström syndrome on chromosome 2p12-13 within a 14.9-cM interval. To confirm this finding in another ethnic population and refine the candidate region we investigated by linkage analysis a consanguineous family of North African origin, in which three of seven siblings displayed all major neurological and metabolic features of Alström syndrome. Genotyping was performed on an ABI377 DNA automatic sequencer and LOD scores were obtained with the Fastlink program. Five markers previously investigated in French Acadians confirmed the involvement of the candidate region, although pairwise LOD scores were of poor significance (Zmax = 2.9). To further confirm homogeneity and refine the candidate region, 20 additional markers were investigated. Haplotype analysis and allele segregation revealed that affected children shared a single haplotype and were homozygous for the eight most centromeric markers (D2S291-D2S2114), over a 6.1-cM interval. Significative multipoint LOD scores (Zmax = 3.96) were obtained between markers D2S2110/145 and D2S286. Two clusters of known genes are present in this refined region of chromosome 2p, the most attractive candidate being the hexokinase II gene. However, except for several known polymorphisms, no mutations were detected in the coding region of this gene. In conclusion, the location of Alström syndrome on chromosome 2p12-13 is confirmed, reducing the genetic interval to 6.1 cM.
- Published
- 1998
- Full Text
- View/download PDF
41. Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance.
- Author
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Rouard M, Macari F, Bouix O, Lautier C, Brun JF, Lefebvre P, Renard E, Bringer J, Jaffiol C, and Grigorescu F
- Subjects
- Amino Acid Sequence, Child, Female, Heterozygote, Humans, Insulin blood, Insulin Receptor Substrate Proteins, Insulin-Like Growth Factor I metabolism, Iodine Radioisotopes, Male, Molecular Sequence Data, Pedigree, Phosphoproteins genetics, Polymorphism, Genetic, Insulin Resistance genetics, Point Mutation, Receptor, Insulin genetics
- Abstract
To elucidate genetic determinants of insulin resistance, we investigated insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) genes, in vitro IR function and in vivo insulin sensitivity in a family with Type A syndrome. Two missense IR mutations (Asp59Gly and Leu62Pro) found in the proband, resulted in reduction by 90% of insulin binding to erythrocytes, decreased receptor autophosphorylation and a dramatic reduction of insulin sensitivity. The proband and mother were heterozygote for Gly972Arg IRS-1 variant. Asp59Gly mutation, also carried by proband's brother with no consequence on insulin sensitivity, was inherited from the mother who is diabetic and insulin resistant and Leu62Pro was from the father. We conclude that severity of insulin resistance in the proband may be explained by the genetic condition of compound heterozygote for IR mutations while severe insulin resistance in the mother raises the possibility that other genetic factors, like IRS-1 polymorphisms, may contribute to the phenotypic expression of IR mutations.
- Published
- 1997
- Full Text
- View/download PDF
42. [Management of care in the child].
- Author
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Lautier C
- Subjects
- Child, Child, Preschool, Humans, Infant, Nurse-Patient Relations, Psychiatric Nursing methods, Touch, Child Psychiatry methods, Psychotherapy methods
- Published
- 1989
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