108 results on '"Sentinelli, F."'
Search Results
2. Circulating miRNA-375 levels are increased in autoantibodies-positive first-degree relatives of type 1 diabetes patients
- Author
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Bertoccini, L., Sentinelli, F., Incani, M., Bailetti, D., Cimini, F. A., Barchetta, I., Lenzi, A., Cavallo, M. G., Cossu, E., and Baroni, M. G.
- Published
- 2019
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3. Positive effects of Nordic Walking on anthropometric and metabolic variables in women with type 2 diabetes mellitus
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Sentinelli, F., La Cava, V., Serpe, R., Boi, A., Incani, M., Manconi, E., Solinas, A., Cossu, E., Lenzi, A., and Baroni, M.G.
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- 2015
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4. The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study
- Author
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Barchetta, I., primary, Dule, S., additional, Bertoccini, L., additional, Cimini, F. A., additional, Sentinelli, F., additional, Bailetti, D., additional, Marini, G., additional, Barbonetti, A., additional, Loche, S., additional, Cossu, E., additional, Cavallo, M. G., additional, and Baroni, M. G., additional
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- 2021
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5. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent
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Romeo, S, Sentinelli, F, Dash, S, Yeo, G S H, Savage, D B, Leonetti, F, Capoccia, D, Incani, M, Maglio, C, Iacovino, M, O'Rahilly, S, and Baroni, M G
- Published
- 2010
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6. Cytokine profile and insulin antibody IgG subclasses in patients with recent onset Type 1 diabetes treated with oral insulin
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Monetini, L., Cavallo, M. G., Sarugeri, E., Sentinelli, F., Stefanini, L., Bosi, E., Thorpe, R., Pozzilli, P., and the Immunotherapy Diabetes (IMDIAB) group
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- 2004
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7. The G972R variant of the insulin receptor substrate-1 (IRS-1) gene is associated with insulin resistance in “uncomplicated” obese subjects evaluated by hyperinsulinemic-euglycemic clamp
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Baroni, M. G., Leonetti, F., Sentinelli, F., Romeo, S., Filippi, E., Fanelli, M., Ribaudo, M. C., Zappaterreno, A., Fallarino, M., and Di Mario, U.
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- 2004
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8. Single-strand conformation polymorphism analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young
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Baroni, M., Sentinelli, F., Massa, O., Romeo, S., Colombo, C., Di Mario, U., and Barbetti, F.
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- 2001
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9. The G972R variant of the Insulin Receptor Substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance
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Baroni, M. G., Arca, M., Sentinelli, F., Buzzetti, R., Capici, F., Lovari, S., Vitale, M., Romeo, S., and Di Mario, U.
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- 2001
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10. Clinical application of best practice guidelines for the genetic diagnosis of MODY2 and MODY3
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Incani, M., Cambuli, V. M., Cavalot, F., Congiu, T., Paderi, M., Sentinelli, F., Romeo, S., Poy, P., Soro, M., Pilia, S., Loche, S., Cossu, E., Trovati, M., Mariotti, S., and Baroni, M. G.
- Published
- 2010
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11. Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the −352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population
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Romeo, S, Sentinelli, F, Cavallo, M G, Leonetti, F, Fallarino, M, Mariotti, S, and Baroni, M G
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- 2008
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12. Deep re-sequencing of 9 type 2 diabetes GWAS loci by comparison of extremes of dynamic indices of insulin secrection
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Bailetti, D., Sentinelli, F., Bertoccini, L., Di Costanzo, A., Incani, M., Arca, M., Leonetti, F., Sabrina Prudente, and Baroni, M.
- Published
- 2017
13. The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children
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Sentinelli, F., primary, Bertoccini, L., additional, Barchetta, I., additional, Capoccia, D., additional, Incani, M., additional, Pani, M.G., additional, Loche, S., additional, Angelico, F., additional, Arca, M., additional, Morini, S., additional, Manconi, E., additional, Lenzi, A., additional, Cossu, E., additional, Leonetti, F., additional, Baroni, M.G., additional, and Cavallo, M.G., additional
- Published
- 2016
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14. Cytokine profile and insulin antibody IgG subclasses in patients with recent onset type 1 diabetes treated with oral insulin
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MONETINI L, CAVALLO MG, SARUGERI E, SENTINELLI F, STEFANINI L, THORPE R, POZZILLI P., BOSI, EMANUELE, Monetini, L, Cavallo, Mg, Sarugeri, E, Sentinelli, F, Stefanini, L, Bosi, Emanuele, Thorpe, R, and Pozzilli, P.
- Published
- 2004
15. Association between CDX2 polymorphism of Vitamin D Receptor (VDR) and type 2 diabetes
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Barchetta, Ilaria, Sentinelli, F., Incani, M., Costantino, C., Pani, M. G., Boi, A., Fraioli, Antonio, Leonetti, Frida, Baroni, Marco Giorgio, and Cavallo, Maria Gisella
- Published
- 2012
16. Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans RID A-1555-2012
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Sentinelli, F, Romeo, S, Maglio, C, Incani, M, Burza, Ma, Scano, F, Coccia, F, Cossu, E, Leonetti, F, and Baroni, M. G.
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- 2011
17. Identification of Sequence Variants in the UBL5 (Ubiquitin-like 5 or BEACON) Gene in Obese Children by PCR-SSCP: No Evidence for Association with Obesity RID A-1555-2012
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Sentinelli, F, Romeo, S, Cambuli, Vm, Cossu, E, Cavallo, Mg, Zavarella, S, Spoletini, M, Buzzetti, R, and Baroni, M. G.
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BMI ,childhood obesity ,PCR-SSCP ,SNP ,high-resolution melting analysis (HRMA) - Published
- 2008
18. Prevalence of maturity onset diabetes of the young (MODY) in Sardinian overweight/obese children not selected according to family history for diabetes
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Baroni, Marco Giorgio, Cambuli, V. M., Romeo, S., Congiu, T., Incani, M., Sentinelli, F., Filetti, Sebastiano, Musiu, M. C., Cavallo, Maria Gisella, Cossu, E., and Loche, S.
- Published
- 2008
19. The Gly482Ser missense mutation of the Peroxisome Proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) gene associates with reduced insulin sensitivity in normal and glucose-intolerant obese subjects
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Fanelli, M, Filippi, E, Sentinelli, F, Romeo, S, Fallarino, M, Buzzetti, R, Leonetti, F, and Baroni, Mg.
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obesity ,PGC-1 alpha gene ,HOMAIR ,BMI (body mass index) ,single nucleotide polymorphisms (SNPs) - Published
- 2005
20. The G972R variant of the insulin receptor substrate-1 (IRS-1) gene is associated with insulin resistance evaluated by clamp in obese subjects without metabolic complications
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Romeo, S, Leonetti, F, Sentinelli, F, Zappaterreno, A, Filippi, E, Banchieri, M, Rossano, S, Di Mario, U, and Baroni, Mg
- Published
- 2003
21. Angiopoietin-like 4 protein (ANGPTL4) E40K protects from developing the atherogenic lipid profile ass in obese individuals
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Romeo, S., primary, Flynn, P., additional, Tan, C.Y., additional, Napolitano, A., additional, Sarker, A., additional, Cox, T.M., additional, Sentinelli, F., additional, Baroni, M.G., additional, and Vidal-Puig, A., additional
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- 2010
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22. Prevalence of Type 1 Diabetes Autoantibodies (GADA, IA2, and IAA) in Overweight and Obese Children
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Cambuli, V. M., primary, Incani, M., additional, Cossu, E., additional, Congiu, T., additional, Scano, F., additional, Pilia, S., additional, Sentinelli, F., additional, Tiberti, C., additional, Cavallo, M. G., additional, Loche, S., additional, and Baroni, M. G., additional
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- 2009
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23. Serum adiponectin is decreased in patients with familial combined hyperlipidemia and normolipaemic relatives and is influenced by lipid-lowering treatment
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Arca, M., primary, Cambuli, V.M., additional, Montali, A., additional, Sentinelli, F., additional, Filippi, E., additional, Campagna, F., additional, Quagliarini, F., additional, Antonini, R., additional, Romeo, S., additional, and Baroni, M.G., additional
- Published
- 2009
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24. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent
- Author
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Romeo, S, primary, Sentinelli, F, additional, Dash, S, additional, Yeo, G S H, additional, Savage, D B, additional, Leonetti, F, additional, Capoccia, D, additional, Incani, M, additional, Maglio, C, additional, Iacovino, M, additional, O'Rahilly, S, additional, and Baroni, M G, additional
- Published
- 2009
- Full Text
- View/download PDF
25. Identification of Sequence Variants in the UBL5 (Ubiquitin-like 5 or BEACON) Gene in Obese Children by PCR-SSCP: No Evidence for Association with Obesity
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Sentinelli, F., primary, Romeo, S., additional, Cambuli, V.M., additional, Cossu, E., additional, Cavallo, M.G., additional, Zavarella, S., additional, Spoletini, M., additional, Buzzetti, R., additional, and Baroni, M.G., additional
- Published
- 2008
- Full Text
- View/download PDF
26. Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the −352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population
- Author
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Romeo, S, primary, Sentinelli, F, additional, Cavallo, M G, additional, Leonetti, F, additional, Fallarino, M, additional, Mariotti, S, additional, and Baroni, M G, additional
- Published
- 2007
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27. The G972R variant of the insulin receptor substrate-1 gene impairs insulin signaling and cell differentiation in 3T3L1 adipocytes; treatment with a PPARγ agonist restores normal cell signaling and differentiation
- Author
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Sentinelli, F, primary, Filippi, E, additional, Cavallo, M G, additional, Romeo, S, additional, Fanelli, M, additional, and Baroni, M G, additional
- Published
- 2006
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28. Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the -352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population.
- Author
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Romeo S, Sentinelli F, Cavallo MG, Leonetti F, Fallarino M, Mariotti S, and Baroni MG
- Published
- 2008
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- View/download PDF
29. The G972R variant of the insulin receptor substrate-1 gene impairs insulin signaling and cell differentiation in 3T3L1 adipocytes; treatment with a PPARγ agonist restores normal cell signaling and differentiation
- Author
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Sentinelli, F, Filippi, E, Cavallo, M G, Romeo, S, Fanelli, M, and Baroni, M G
- Abstract
The insulin receptor substrate-1 (IRS-1) plays a central role in insulin sensitivity, and association studies have shown that the IRS-1 G972R variant is a risk factor for insulin resistance. However, how this mutation may lead to impaired insulin sensitivity is still to be determined. Our study aimed to evaluate, after transfection of the IRS-1 G972R variant in 3T3L1 adipocytes, the effect of this mutation on insulin signaling and on cell differentiation. The 3T3L1 cells were transfected with pcDNA3 expression vector containing either the human wild-type IRS-1 or the G972R variant. After induction of differentiation, the 3T3L1 transfected with wild-type IRS-1 differentiated in 6–8 days, while the cells transfected with G972R variant did not differentiate. To determine whether the defect in IRS-1 was responsible for this, we analyzed the expression of several genes involved in the insulin signaling pathway. Results showed that PPARγ expression was significantly reduced in cells transfected with the mutated IRS-1, together with a significant decrease in binding of phosphatidylinositol-3 kinase (PI 3-kinase) to IRS-1 G972R and in PI 3-kinase activity. In addition, we observed that the interaction between the insulin receptor (IR) and the IRS-1 G972R protein was increased and that the autophosphorylation of the IR was significantly inhibited in 3T3L1-G972R cells compared with 3T3L1-WT. Treatment of the 3T3L1-G972R cells with pioglitazone (PIO), a PPARγ agonist, restored differentiation with higher level of PPARγ expression and restoration of PI 3-kinase binding to IRS-1 G972R and PI 3-kinase activity. IR autophosphorylation was also increased. Withdrawal of PIO in fully differentiated 3T3L1-G972R cells determined the reappearance of the insulin signaling defect. Finally, we observed higher levels of IRS-2 expression, suggesting that IRS-2 may play a more important role in adipocyte insulin signaling. In conclusion, IRS-1 G972R variant impairs insulin signaling, and treatment with PPARγ agonist restores the normal phenotype of 3T3L1 cells.
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- 2005
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30. The G972Rvariant of the insulin receptor substrate-1 (IRS-1)gene is associated with insulin resistance in “uncomplicated” obese subjects evaluated by hyperinsulinemic-euglycemic clamp
- Author
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Baroni, M., Leonetti, F., Sentinelli, F., Romeo, S., Filippi, E., Fanelli, M., Ribaudo, M., Zappaterreno, A., Fallarino, M., and Mario, U.
- Abstract
Several association studies have indicated the insulin receptor substrate-1(IRS-1) gene G972Rvariant as a genetic risk factor for insulin resistance, particularly in presence of obesity. A few studies have also suggested a possible effect of the G972Rvariant on insulin secretion. The aim of this study was to evaluate the role of the IRS-1gene G972Rvariant in 61 subjects with “uncomplicated” obesity [i.e. without diabetes, hypertension, dyslipidemia, coronary artery disease (CAD)], studied by hyperinsulinemic-euglycemic clamp. The presence of the G972Rvariant, detected in real-time with LightCycler hybridisation probes, was related to the indexes of insulin sensitivity. Furthermore, the possible role of this variant on insulin secretion was studied by means of insulin release indexes derived from oral tolerance test (OGTT). Twenty-four point five percent (24.5%) (no.=15) of the obese subjects proved to be carriers of the G972Rvariant. M index (p<0.05), non-oxidative glucose (p<0.01), insulin clearance (p<0.03) and insulin sensitivity index (ISI) (p<0.005) were all significantly reduced in G972Rcarriers compared to non-carriers, indicating a significant reduction in insulin sensitivity in carriers of the variant. A logistic regression analysis confirmed the independent association between the G972Rvariant and reduced insulin sensitivity (p<0.03). The interaction between obesity and the G972Rvariant was also independently associated with a reduced insulin sensitivity (p<0.005), suggesting that obesity and G972Rvariant were more than additive in predicting insulin resistance. The analysis of insulin release indexes did not show any significant differences. Our results demonstrate the association of the G972Rvariant of the IRS-1gene with reduced insulin sensitivity in obese subjects, and indicate a possible interaction between the IRS-1variant and obesity in worsening of insulin sensitivity.
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- 2004
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31. A simple method for non-radioactive PCR-SSCP using MDE gel solution and a midi gel format
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Sentinelli, F., Lovari, S., Vitale, M., Giorgi, G., Mario, U. Di, and Baroni, M. G.
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- 2000
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32. 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. 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- 1999
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33. 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. J., Darville, M. I., Ho, Y-S, Sternesjo, J., Sandler, S., Chen, M-C, Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Breant, 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., 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, 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., 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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T., Kardos, A., Gingl, Z., Kempler, P., Rudas, L., Lonovics, J., Marchand, M., Stevens, L. K., Tarnas, Gy, Eurodiab Iddm, Study Group, Estrella, F., Christensen, N. J., Keresztes, K., Barna, I., Hermanyi, Zs, Vargha, P., Bonnevie, L., Chanudet, X., Larroque, P., Tutuncu, N. Bascil, Deger, A., Batur, M. K., Yildirir, A., Onalan, O., Aksoyek, S., Kabakciota, G., Erbas, T., Galicka-Latala, D., Surdacki, A., Gerritsen, J., Tenvoorde, B. J., Heethaar, R. M., Tagawa, T. S., Kodama, M., Yoshioka, R., Yamasaki, Y., Didangelos, T., Athyros, V., Kontopoulos, A., Papageorgiou, A., Karamitsos, D., Lacigova, S., Rusavy, Z., Karova, R., Perrild, H., Kay, L., Jorgensen, T., Bien, A. I., Witek, P., Geraldes, Elizabete, Rodrigues, D., Pereira, L., Domenech, A., Leitao, P., Anagnostopoulos, D., Foster, A. V. M., Nag, S., Barsoum, M., Lewis, G., Dunlop, N., Connolly, V., Bilous, R., Kelly, W., Chantelau, E., Gede, A., Sharman, D., O Halloran, D., Best, C., Abbas, Z. G., Lutale, J., Gill, G. V., Jarvis, W. R., Archibald, L. K., Corcoran, S., Mansell, J., Pibworth, L., Terada, H., Shiba, T., Utugi, N., Utugi, T., Blum, M., Strobel, J., Hoffken, K., Razvi, F. M., Kritzinger, E. E., Taylor, K., Jones, S., Illahi, W., Grubetaer, M., Hartmann, P., Hoffstadt, K., Leiden, H. A., Moll, A. C., Polak, B. C. P., Pietragalla, G. B., Maurino, M., Montanaro, M., Karadeniz, S., Tommasini, P., Quadrini, C., Demiraj, V., Rispoli, E., Ota, A., Takama, H., Saito, N., Hemandez, C., Lepore, D., Antico, L., Giardina, B., Franconi, F., Michoud, E., Chamot, S., Riva, Ch, Hammes, H-P, Renner, O., Breier, G., Lin, J., Alt, A., Betzholtz, C., Bretzel, R. G. Rd, Manti, R., Gallo, M., Molinar Hin, A., Brignardello, E., Boccuzzi, G., Li, Shanfang, Xiang, Kunsan, Zhang, Rugeng, Shangguan, Xinhong, Wu, Jianrong, Donnan, P. T., Broomhall, J., Hunter, K., Morris, A. 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34. The Gly482Ser missense mutation of the Peroxisome Proliferator - Activated receptor γ coactivator - 1α (PGC - 1α) gene associates with reduced insulin sensitivity in normal and glucose-intolerant obese subjects
- Author
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Fanelli, M., Filippi, E., Sentinelli, F., Romeo, S., Fallarino, M., Buzzetti, R., Frida LEONETTI, and Baroni, M. G.
35. Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes
- Author
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Bertoccini, Laura, Bailetti, Diego, SUMMER Study in Diabetes Group (Summer, Alessi, Elena, Bagella, FRANCESCO MARIA, Barchetta, Ilaria, Capoccia, Danila, Silvia, Carletti, Coccia, Federica, Conti, Francesco, D'Onofrio, Luca, Filardi, Tiziana, Giulia, Leanza, Gianluca, Margiotta, Incani, Michela, Moretti, Chiara, Pezzilli, Serena, Pibiri, Carlotta, Pamela, Piscitelli, Maria Giovanna Scarale, Sentinelli, Federica, Tavaglione, Federica, Buzzetti, Raffaella, Cavallo, Maria Gisella, Copetti, Massimiliano, Cossu, Efisio, D'Angelo, Paola, De Cosmo, Salvatore, Di Mauro, Lazzaro, Leonetti, Frida, Morano, Susanna, Morviducci, Lelio, Napoli, Nicola, Prudente, Sabrina, Pugliese, Giuseppe, Trischitta, Vincenzo, Baroni Marco, Giorgio., Bertoccini, L., Bailetti, D., Buzzetti, R., Cavallo, M. G., Copetti, M., Cossu, E., D'Angelo, P., De Cosmo, S., Di Mauro, L., Leonetti, F., Morano, S., Morviducci, L., Napoli, N., Prudente, S., Pugliese, G., Trischitta, V., Baroni, M. G., Alessi, E., Bagella, F., Barchetta, I., Capoccia, D., Carletti, S., Coccia, F., Conti, F., D'Onofrio, L., Filardi, T., Leanza, G., Margiotta, G., Incani, M., Moretti, C., Pezzilli, S., Pibiri, C., Piscitelli, P., Scarale, M. G., Sentinelli, F., and Tavaglione, F.
- Subjects
medicine.medical_specialty ,Population ,Type 2 diabetes ,030204 cardiovascular system & hematology ,genetic risk score ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Genotype ,medicine ,Vitamin D and neurology ,030212 general & internal medicine ,education ,Gene ,education.field_of_study ,Framingham Risk Score ,CYP2R1 (Cytochrome P450 Family 2 Subfamily R Member 1) ,business.industry ,GC (Vitamin D Binding Protein) ,Mortality rate ,DHCR7 (7-dehydrocholesterol reductase) ,medicine.disease ,Genetic risk score ,Endocrinology ,Oncology ,SUMMER Study in Diabetes ,business ,Research Paper - Abstract
Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by EcoTM Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 × 10-4) and GC rs4588 (p = 1 × 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 × 10-11) and insufficiency (
- Published
- 2018
36. Renal Expression and Localization of the Receptor for (Pro)renin and Its Ligands in Rodent Models of Diabetes, Metabolic Syndrome, and Age-Dependent Focal and Segmental Glomerulosclerosis.
- Author
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Iacobini C, Vitale M, Sentinelli F, Haxhi J, Pugliese G, and Menini S
- Subjects
- Mice, Animals, Humans, Renin genetics, Renin metabolism, Rodentia metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Kidney metabolism, Ligands, Metabolic Syndrome metabolism, Diabetes Mellitus, Experimental metabolism, Kidney Diseases metabolism, Glomerulosclerosis, Focal Segmental
- Abstract
The (pro)renin receptor ((P)RR), a versatile protein found in various organs, including the kidney, is implicated in cardiometabolic conditions like diabetes, hypertension, and dyslipidemia, potentially contributing to organ damage. Importantly, changes in (pro)renin/(P)RR system localization during renal injury, a critical information base, remain unexplored. This study investigates the expression and topographic localization of the full length (FL)-(P)RR, its ligands (renin and prorenin), and its target cyclooxygenase-2 and found that they are upregulated in three distinct animal models of renal injury. The protein expression of these targets, initially confined to specific tubular renal cell types in control animals, increases in renal injury models, extending to glomerular cells. (P)RR gene expression correlates with protein changes in a genetic model of focal and segmental glomerulosclerosis. However, in diabetic and high-fat-fed mice, (P)RR mRNA levels contradict FL-(P)RR immunoreactivity. Research on diabetic mice kidneys and human podocytes exposed to diabetic glucose levels suggests that this inconsistency may result from disrupted intracellular (P)RR processing, likely due to increased Munc18-1 interacting protein 3. It follows that changes in FL-(P)RR cellular content mechanisms are specific to renal disease etiology, emphasizing the need for consideration in future studies exploring this receptor's involvement in renal damage of different origins.
- Published
- 2024
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- View/download PDF
37. Reduced Lipopolysaccharide-Binding Protein (LBP) Levels Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Adipose Inflammation in Human Obesity.
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Barchetta I, Cimini FA, Sentinelli F, Chiappetta C, Di Cristofano C, Silecchia G, Leonetti F, Baroni MG, and Cavallo MG
- Subjects
- Humans, Adult, Middle Aged, Lipopolysaccharides metabolism, Cross-Sectional Studies, Obesity metabolism, Liver metabolism, Inflammation metabolism, Non-alcoholic Fatty Liver Disease metabolism, Diabetes Mellitus, Type 2 metabolism
- Abstract
Lipopolysaccharide (LPS) and its binding protein LBP have emerged as potential contributors to the progression from overweight/obesity to overt metabolic diseases and NAFLD. While LPS is known to activate hepatocyte inflammation, thus contributing toward NAFLD development, the role of LBP is more intricate, and recent data have shown that experimental reduction in hepatic LBP promotes NAFLD progression. In this cross-sectional investigation, we evaluated circulating LBP in relation to obesity, NAFLD, visceral adipose tissue (VAT) inflammation, and type 2 diabetes (T2D). We recruited 186 individuals (M/F: 81/105; age: 47 ± 10.4 years; BMI: 35.5 ± 8.6 kg/m
2 ); a subgroup ( n = 81) underwent bariatric surgery with intra-operative VAT and liver biopsies. LBP levels were higher in obese individuals than non-obese individuals but were inversely correlated with the parameters of glucose metabolism. Reduced LBP predicted T2D independent of age, sex, and BMI ( p < 0.001). LBP levels decreased across more severe stages of hepatosteatosis and lobular inflammation, and were inversely associated with VAT inflammation signatures. In conclusion, LBP levels are increased in obese individuals and are associated with a more favorable metabolic profile and lower NAFLD/NASH prevalence. A possible explanation for these findings is that hepatic LBP production may be triggered by chronic caloric excess and facilitate LPS degradation in the liver, thus protecting these individuals from the metabolic consequences of obesity.- Published
- 2023
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38. Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children.
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Sentinelli F, Barchetta I, Cimini FA, Dule S, Bailetti D, Cossu E, Barbonetti A, Totaro M, Melander O, Cavallo MG, and Baroni MG
- Subjects
- Adolescent, Humans, Child, Neurotensin genetics, Neurotensin metabolism, Overweight genetics, Fatty Acids, Insulin Resistance genetics, Pediatric Obesity
- Abstract
Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels of its precursor, pro-NT, predicts the presence and development of metabolic and cardiovascular diseases. Despite the extensive knowledge on the dynamic changes that occur to pro-NT = after fat load, the determinants of fasting pro-NT are unknown. The aim of this study was to determine the possible genetic regulation of plasma pro-NT. The NT gene (NTS) was sequenced for potential functional variants, evaluating its entire genomic and potentially regulatory regions, in DNA from 28 individuals, stratified by low and high pro-NT levels. The identified variant differently distributed in the two pro-NT subgroups was genotyped in a cohort of nine hundred and thirty-two overweight/obese children and adolescents. A total of seven sequence variations across the NTS gene, none of them located in coding regions, were identified. The rs2234762 polymorphism, sited in the NTS gene promoter, was statistically more frequent in the lowest pro-NTS level group. Carriers of the rs2234762 variant showed lower pro-NT levels, after adjusting for sex, age, BMI, triglycerides and the Tanner stage. Having NTS rs2234762 predicted less pronounced insulin resistance at the 6.5-year follow-up with OR: 0.46 (0.216-0.983), at the logistic regression analysis adjusted for age, sex and BMI. In conclusion, the NTS rs2234762 gene variant is a determinant of reduced circulating pro-NT levels in overweight and obese children, which predisposes this group to a more favorable metabolic profile and a reduced insulin resistance later in life, independently from metabolic confounders.
- Published
- 2023
- Full Text
- View/download PDF
39. Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans.
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Bailetti D, Sentinelli F, Prudente S, Cimini FA, Barchetta I, Totaro M, Di Costanzo A, Barbonetti A, Leonetti F, Cavallo MG, and Baroni MG
- Subjects
- Adult, Cohort Studies, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 pathology, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Carrier Proteins genetics, Diabetes Mellitus, Type 2 epidemiology, GTPase-Activating Proteins genetics, Insulin Resistance, Insulin Secretion, Obesity physiopathology, Polymorphism, Single Nucleotide, RNA-Binding Proteins genetics
- Abstract
Type 2 diabetes is characterized by impairment in insulin secretion, with an established genetic contribution. We aimed to evaluate common and low-frequency (1-5%) variants in nine genes strongly associated with insulin secretion by targeted sequencing in subjects selected from the extremes of insulin release measured by the disposition index. Collapsing data by gene and/or function, the association between disposition index and nonsense variants were significant, also after adjustment for confounding factors (OR = 0.25, 95% CI = 0.11-0.59, p = 0.001). Evaluating variants individually, three novel variants in ARAP1, IGF2BP2 and GCK , out of eight reaching significance singularly, remained associated after adjustment. Constructing a genetic risk model combining the effects of the three variants, only carriers of the ARAP1 and IGF2BP2 variants were significantly associated with a reduced probability to be in the lower, worst, extreme of insulin secretion (OR = 0.223, 95% CI = 0.105-0.473, p < 0.001). Observing a high number of normal glucose tolerance between carriers, a regression posthoc analysis was performed. Carriers of genetic risk model variants had higher probability to be normoglycemic, also after adjustment (OR = 2.411, 95% CI = 1.136-5.116, p = 0.022). Thus, in our southern European cohort, nonsense variants in all nine candidate genes showed association with better insulin secretion adjusted for insulin resistance, and we established the role of ARAP1 and IGF2BP2 in modulating insulin secretion.
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- 2022
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40. Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease.
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Barchetta I, Ceccarelli V, Cimini FA, Barone E, Sentinelli F, Coluzzi M, Chiappetta C, Bertoccini L, Tramutola A, Labbadia G, Di Cristofano C, Silecchia G, Leonetti F, and Cavallo MG
- Subjects
- Bariatric Surgery methods, Biomarkers blood, Biomarkers metabolism, Biopsy methods, Cardiometabolic Risk Factors, Cost-Benefit Analysis, Disease Progression, Female, Humans, Italy epidemiology, Male, Middle Aged, Monitoring, Physiologic methods, Patient Acuity, Risk Assessment methods, Dipeptidyl Peptidase 4 blood, Dipeptidyl Peptidase 4 metabolism, Liver metabolism, Liver pathology, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Obesity diagnosis, Obesity epidemiology, Obesity metabolism, Obesity surgery
- Abstract
Introduction: Dipeptidyl peptidase 4 (DPP4) levels are associated to metabolic and cardiovascular diseases in humans; initial evidence reported a relationship between DPP4 and chronic liver diseases. Aim of this study was to investigate hepatic and systemic DPP4 levels/activity in relation to NAFLD/NASH in individuals with and without metabolic disease., Methods: We recruited fifty-two obese individuals undergoing bariatric surgery and intra-operative liver biopsy at Sapienza University, Rome, Italy. The association between DPP4 levels/activity and NAFLD was also evaluated in 126 non-obese individuals recruited in the same setting., Results: NAFLD patients had significantly higher circulating DPP4 activity than no-NAFLD in both the obese and non-obese cohorts; plasma DPP4 activity and levels linearly correlated with steatosis grade and inflammation at the liver biopsy. Hepatic DPP4 mRNA was not associated to either its circulating levels/activity or NAFLD. In the multivariate logistic regression analysis on all the study participants (n = 178), higher circulating DPP4 activity was associated with NAFLD independently of potential confounders with OR (95% CI): 3.5 (1.2-10.21), p = 0.022., Conclusions: This study demonstrates the coexistence of increased plasma DPP4 levels and activity in NAFLD. Circulating DPP4 measurement may represent a novel cost-effective strategy for NAFLD/NASH risk stratification and a potential tool for monitoring disease's progression in established NAFLD.
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- 2021
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41. Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children.
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Barchetta I, Bertoccini L, Sentinelli F, Bailetti D, Marini G, Cimini FA, Ceccarelli V, Struck J, Schulte J, Loche S, Cossu E, Melander O, Cavallo MG, and Baroni MG
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- Age Factors, Biomarkers blood, Child, Female, Humans, Longitudinal Studies, Male, Metabolic Diseases diagnosis, Metabolic Diseases physiopathology, Pediatric Obesity diagnosis, Pediatric Obesity physiopathology, Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, Up-Regulation, Energy Metabolism, Metabolic Diseases blood, Neurotensin blood, Pediatric Obesity blood, Protein Precursors blood, Weight Gain
- Abstract
Background and Aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life., Methods and Results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036)., Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
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- 2021
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42. Granzyme B Expression in Visceral Adipose Tissue Associates With Local Inflammation and Glyco-Metabolic Alterations in Obesity.
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Cimini FA, Barchetta I, Ceccarelli V, Chiappetta C, Di Biasio A, Bertoccini L, Sentinelli F, Leonetti F, Silecchia G, Di Cristofano C, Baroni MG, Velotti F, and Cavallo MG
- Subjects
- Adult, Female, Glucose metabolism, Granzymes genetics, Humans, Inflammation blood, Inflammation genetics, Male, Metabolic Diseases blood, Metabolic Diseases genetics, Middle Aged, Obesity genetics, Granzymes blood, Intra-Abdominal Fat metabolism, Obesity blood
- Abstract
Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with "sick" fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases., (Copyright © 2020 Cimini, Barchetta, Ceccarelli, Chiappetta, Di Biasio, Bertoccini, Sentinelli, Leonetti, Silecchia, Di Cristofano, Baroni, Velotti and Cavallo.)
- Published
- 2020
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43. Association of Apelin Levels in Overweight-obese Children with Pubertal Development, but Not with Insulin Sensitivity: 6.5 Years Follow up Evaluation.
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Sentinelli F, Bertoccini L, Incani M, Pani MG, David F, Bailett D, Boi A, Barchetta I, Cimini FA, Mannino AC, Lenzi A, Cavallo MG, Loche S, Cossu E, and Baroni MG
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- Adolescent, Age Factors, Child, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Male, Pediatric Obesity blood, Sex Factors, Adolescent Development physiology, Apelin blood, Insulin Resistance physiology, Overweight blood, Puberty physiology
- Abstract
Background: Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited., Objective: We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes., Methods: Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method., Results: At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p < .002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p < .001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity., Conclusions: Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the "physiological" insulin resistance of puberty. Abbreviations : ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides.
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- 2020
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44. Greater circulating DPP4 activity is associated with impaired flow-mediated dilatation in adults with type 2 diabetes mellitus.
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Barchetta I, Ciccarelli G, Barone E, Cimini FA, Ceccarelli V, Bertoccini L, Sentinelli F, Tramutola A, Del Ben M, Angelico F, Baroni MG, Lenzi A, and Cavallo MG
- Subjects
- Adult, Aged, Biomarkers blood, Brachial Artery enzymology, Case-Control Studies, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 enzymology, Endothelium, Vascular enzymology, Female, Humans, Male, Middle Aged, Rome, Up-Regulation, Brachial Artery physiopathology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 physiopathology, Dipeptidyl Peptidase 4 blood, Endothelium, Vascular physiopathology, Vasodilation
- Abstract
Background and Aim: Dipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in experimental models. The relationship between DPP4 activity and endothelial function in diabetes has not been explored yet. Aim of this study was to investigate systemic plasma DPP4 activity in relation to endothelial function in patients with type 2 diabetes mellitus (T2DM)., Methods and Results: Sixty-two T2DM individuals were recruited in our Diabetes outpatient clinics, Sapienza University, Rome, Italy. All participants underwent complete clinical work-up; endothelial function was evaluated by flow-mediated dilatation (FMD) test; plasma DPP4 activity was assessed by measuring the 7-amino-4-methylcoumarin (AMC) cleavage rate from the synthetic substrate H-glycyl-prolyl-AMC and compared with DPP4 activity measured in sixty-two age-, sex-, BMI-matched non-diabetic subjects. Patients with T2DM had significantly higher DPP4 activity than non-diabetic individuals (211,466 ± 87657 vs 158,087 ± 60267 nmol/min/ml, p < 0.001); in T2DM patients, greater DPP4 activity significantly correlated with lower FMD whereas was not associated with BMI and metabolic control. Greater systemic DPP4 activity was an independent predictor of reduced FMD after adjusting for age, gender and other confounders., Conclusions: Circulating DPP4 activity is increased in individuals with T2DM and associated with signs of endothelial dysfunction such as impaired FMD. DPP4 may negatively affect endothelial function through mechanisms beyond glucose homeostasis and metabolic control., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)
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- 2019
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45. The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus.
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Bertoccini L, Sentinelli F, Leonetti F, Bailetti D, Capoccia D, Cimini FA, Barchetta I, Incani M, Lenzi A, Cossu E, Cavallo MG, and Baroni MG
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- 25-Hydroxyvitamin D 2 blood, Adult, Calcifediol blood, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 metabolism, Female, Genetic Association Studies, Humans, Italy, Male, Receptors, Calcitriol metabolism, Reproducibility of Results, Diabetes Mellitus, Type 2 genetics, Polymorphism, Single Nucleotide, Receptors, Calcitriol genetics
- Abstract
Aim: Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls., Materials and Methods: For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated., Results: Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes., Conclusions: Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.
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- 2017
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46. The Arg282Ser missense mutation in APOA5 gene determines a reduction of triglyceride and LDL-cholesterol in children, together with low serum levels of apolipoprotein A-V.
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Bertoccini L, Sentinelli F, Incani M, Bailetti D, Cimini FA, Barchetta I, Cavallo MG, Cossu E, Lenzi A, Loche S, and Baroni MG
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- Adolescent, Alleles, Apolipoprotein A-V genetics, Child, Cholesterol, HDL blood, Cohort Studies, Female, Gene Expression, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Obesity blood, Obesity pathology, Apolipoprotein A-V blood, Cholesterol, LDL blood, Mutation, Missense, Obesity genetics, Triglycerides blood
- Abstract
Background: Apolipoprotein A-V (ApoA-V) is a recognized regulator of plasma triglycerides (TGs), and previous studies have shown associations between variants in APOA5 (apolipoprotein-A5) gene and high TG levels. Recently, a new association between the Arg282Ser missense mutation (rs778114184 G > T) in APOA5 gene and decreased triglyceride levels has been shown in an adult population from Sardinia. In this study we add further insight into the role of APOA5 by exploring whether this association begins early in life in children, or becomes manifest only in adulthood. We performed the genetic association analysis of APOA5 in a cohort of 925 overweight and obese children and adolescents from Sardinia, Italy, to see if the genetic burden is already at play before modifying risk factors are interacting., Results: We identified 24 heterozygous subjects for the Arg282Ser variant and no homozygous subject. Here we show that the Arg282Ser mutation in APOA5 gene is associated with a significant reduction of TG (-15.5 mg/dl), total (-18.1 mg/dl) and LDL-cholesterol (-14.8 mg/dl) levels in overweight/obese children and adolescents, indicating that indeed this association appears early in life. Also, we observed a significant reduction in serum apoA-V levels in heterozygous children., Conclusions: Our data clearly show that the Arg282Ser mutation in APOA5 gene determines a reduction of TG, total and LDL-cholesterol and apolipoprotein A-V levels in overweight/obese children and adolescents, demonstrating that this mutation has the power to affect lipid levels already since childhood.
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- 2017
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47. The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects.
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Sentinelli F, Capoccia D, Incani M, Bertoccini L, Severino A, Pani MG, Manconi E, Cossu E, Leonetti F, and Baroni MG
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- Biomarkers analysis, Blood Glucose analysis, Diabetes Mellitus metabolism, Diabetes Mellitus pathology, Female, Follow-Up Studies, Glycated Hemoglobin analysis, Humans, Insulin genetics, Insulin Secretion, Male, Middle Aged, Prognosis, Diabetes Mellitus etiology, Insulin metabolism, Insulin Resistance genetics, Mutation, Missense genetics, Obesity complications, Perilipin-2 genetics
- Abstract
Background: Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia., Methods: A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants., Results: We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin-sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender-specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild-type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed., Conclusion: We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)
- Published
- 2016
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48. Search for Genetic Variant in the Apelin Gene by Resequencing and Association Study in European Subjects.
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Sentinelli F, Capoccia D, Bertoccini L, Barchetta I, Incani M, Coccia F, Manconi E, Lenzi A, Cossu E, Leonetti F, Cavallo MG, and Baroni MG
- Subjects
- Adult, Apelin, Diabetes Mellitus, Type 2 blood, Female, High-Throughput Nucleotide Sequencing, Humans, Intercellular Signaling Peptides and Proteins blood, Italy, Male, Middle Aged, Diabetes Mellitus, Type 2 genetics, Intercellular Signaling Peptides and Proteins genetics, Polymorphism, Single Nucleotide
- Abstract
Aims: Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants., Methods: We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency >0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits., Results: Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits., Conclusions: Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.
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- 2016
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49. Transmembrane-6 superfamily member 2 (TM6SF2) E167K variant increases susceptibility to hepatic steatosis in obese children.
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Mancina RM, Sentinelli F, Incani M, Bertoccini L, Russo C, Romeo S, and Baroni MG
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- Fatty Liver diagnostic imaging, Female, Genotype, Humans, Italy epidemiology, Male, Obesity epidemiology, Prevalence, Ultrasonography, Fatty Liver epidemiology, Fatty Liver genetics, Genetic Predisposition to Disease epidemiology, Membrane Proteins genetics
- Published
- 2016
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50. Glycated hemoglobin for the diagnosis of diabetes and prediabetes: Diagnostic impact on obese and lean subjects, and phenotypic characterization.
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Incani M, Sentinelli F, Perra L, Pani MG, Porcu M, Lenzi A, Cavallo MG, Cossu E, Leonetti F, and Baroni MG
- Abstract
Aims/introduction: Measurement of glycated hemoglobin (HbA1c) has been recommended for the diagnosis of diabetes and prediabetes. However, epidemiological studies have shown significant discordance between HbA1c and glucose-based tests. Of the factors that could influence agreement between HbA1c and the oral glucose tolerance test (OGTT), bodyweight has not been fully evaluated. The aims of the present study were to evaluate the impact of HbA1c criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine HbA1c in relation to body mass index., Materials and Methods: Two cohorts were studied, one from an obesity clinic (n = 592) and one from subjects undergoing screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement., Results: In the obese cohort, HbA1c ≥6.5% (≥48 mmol/mol) showed a sensitivity of 69.3% for diabetes, whereas HbA1c 5.7-6.4% (39-46 mmol/mol) did not identify prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c had low sensitivities for both diabetes (39.2%) and prediabetes (53.3%). When participants were stratified according to body mass index class I-III, HbA1c agreement with the OGTT for diabetes was much higher (80%, P < 0.005) in class I obesity compared with class II-III obesity; whereas for prediabetes, HbA1c had a low sensitivity in all obesity classes., Conclusions: The agreement between HbA1c, fasting plasma glucose and 2-h glucose post-OGTT for the diagnosis of prediabetes was poor in our Italian population; whereas HbA1c ≥6.5% showed a relatively good agreement with OGTT for the diagnosis of diabetes. For the first time, we have shown that obesity class influences the diagnostic performance of HbA1c.
- Published
- 2015
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