المؤلفون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lars, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.

المساهمون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lar, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.

مصطلحات موضوعية: CD274, Immune checkpoint inhibitor, IRF1, Pancreatic beta cell, Pancreatic islet, PDL-1, PDL1, Type 1 diabete, Adolescent, Adult, B7-H1 Antigen, Biomarker, Cell Line, Child, Preschool, Diabetes Mellitus, Type 1, Human, Insulin-Secreting Cell, Interferon Regulatory Factor-1, Interferon-alpha, Interferon-gamma, Islets of Langerhan, Middle Aged, Young Adult, Gene Expression Regulation, Biochemistry, Genetics and Molecular Biology (all)

الوصف: Background: Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated. Methods: The expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot. Specific and previously validated small interference RNAs were used to inhibit STAT1, STAT2, IRF1 and JAK1 signaling. Key results were validated using the JAK inhibitor Ruxolitinib. Findings: PDL1 was present in insulin-positive cells from twelve T1D individuals (6 living and 6 deceased donors) but absent from insulin-deficient islets or from the islets of six non-diabetic controls. Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT1 or STAT2 individually did not prevent interferon-α-induced PDL1, while blocking of JAKs – a proposed therapeutic strategy for T1D – or IRF1 prevented PDL1 induction. Interpretation: These findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons via IRF1.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30269996; info:eu-repo/semantics/altIdentifier/wos/WOS:000447685300041; volume:36; firstpage:367; lastpage:375; numberofpages:9; journal:EBIOMEDICINE; info:eu-repo/grantAgreement/EC/H2020/115797 667191; http://hdl.handle.net/11568/954955Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85054193057; https://www.sciencedirect.com/science/article/pii/S2352396418303980Test

الإتاحة: https://doi.org/10.1016/j.ebiom.2018.09.040Test
http://hdl.handle.net/11568/954955Test
https://www.sciencedirect.com/science/article/pii/S2352396418303980Test

المؤلفون: CRISCI, ISABELLA, Aragona, Michele, Politi, Konstantina Savvina, DANIELE, GIUSEPPE, DEL PRATO, STEFANO

المساهمون: Crisci, Isabella, Aragona, Michele, Politi, Konstantina Savvina, Daniele, Giuseppe, DEL PRATO, Stefano

مصطلحات موضوعية: Continuous glucose monitoring, Glycemic variability, Insulin pump therapy, Liraglutide, Type 1 diabete, Adult, Aged, Area Under Curve, Blood Glucose, Body Mass Index, C-Peptide, Diabetes Mellitus, Type 1, Female, Glucagon-Like Peptide-1 Receptor, Hemoglobin A, Glycosylated, Human, Hypoglycemia, Hypoglycemic Agent, Male, Middle Aged, Endocrinology, Internal Medicine, Diabetes and Metabolism

الوصف: Aims: To test potential efficacy of liraglutide, a GLP-1 receptor agonist, in subjects with type 1 diabetes (T1DM). Methods: We have recruited nine T1DM patients (age 40.1±6.4years, duration of diabetes 19.2±8.8years, BMI 24.3±3.5kg/m2, HbA1c 8.2±1.0%–66±11mmol/mol, daily insulin dose: 0.6±0.1IU/kg) on continuous subcutaneous insulin therapy with undetectable C-peptide. In addition to existing treatment was administered in single-blind (a) therapy subcutaneously with 0.1ml of saline solution for 3days and (b) 0.1ml of liraglutide (0.6mg/day) for a further 3days with daily glucose excursions recorded by continuous glucose monitoring. Results: Adding liraglutide resulted in a significant reduction in mean blood glucose (138±29 vs. 163±29mg/dl, p<0.0001) and standard deviation (42±9 vs. 60±15mg/dl, p<0.0001). The area under the curve (AUC) for blood glucose >140mg/dl was also significantly reduced (22.2±16.4 vs. 41.1±19.7mg/dlh, p<0.05) with no difference in AUC for blood glucose <70mg/dl (liraglutide 0.7±0.9mg/dlh; placebo: 0.8±1.4mg/dlh, p=NS). Finally, adding liraglutide reduced daily insulin requirement (37.5±17.2 vs. 42.9±22.4 UI/day, p<0.01). Conclusions: Short-term treatment with liraglutide, in T1DM, reduces average blood glucose, blood glucose variability and daily insulin requirement without increasing risk of hypoglycemia.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26293127; info:eu-repo/semantics/altIdentifier/wos/WOS:000363950500014; volume:52; issue:6; firstpage:1129; lastpage:1133; numberofpages:5; journal:ACTA DIABETOLOGICA; http://hdl.handle.net/11568/763653Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84945461146; link.springer.de/link/service/journals/00592/index.htm

الإتاحة: https://doi.org/10.1007/s00592-015-0800-6Test
http://hdl.handle.net/11568/763653Test

المؤلفون: Peeters, Stijn A., Engelen, Lian, Buijs, Jacqueline, Chaturvedi, Nish, Fuller, John H., Schalkwijk, Casper G., Stehouwer, Coen D, Karamanos, B., Kofinis, A., Petrou, K., Giorgino, F., Picca, G., Angarano, A., Null, de P.e.r.g.o.l.a. G., Laviola, L., Giorgino, R., Ionescu Tirgoviste, C., Coszma, A., Guja, C., Songini, M., Casu, A., Pedron, M., Pintus, S., Fossarello, M., Ferriss, J. B., Grealy, G., O'Keefe, D., Toeller, M., Arden, C., Rottiers, R., Tuyttens, C., Priem, H., Ebeling, P., Kylliainen, M., Koivisto, V. A., Idzior Walus, B., Sieradzki, J., Cyganek, K., Solnica, B., Lemkes, H. H. P. J., Lemkes Stuffken, J. C., Nunes Correa, J., Rogado, M. C., Gardete Correia, L., Cardoso, M. C., Silva, A., Boavida, J., Machado Sa Marques, M., Michel, G., Wirion, R., Cardillo, S., Pozza, G., Mangili, R., Asnaghi, V., Standl, E., Schaffler, B., Brand, H., Harms, A., Ben Soussan, M., Verier Mine, O., Fallas, P., Fallas, M. C., Fuller, J. H., Holloway, J., Asbury, L., Betteridge, D. J., Cathelineau, G., Bouallouche, A., Villatte Cathelineau, B., Santeusanio, F., Rosi, G., D'Alessandro, V., Cagini, C., Bottini, P., Reboldi, G. P., Navalesi, R., Bandinelli, S., Ghirlanda, G., Saponara, C., Cotroneo, P., Manto, A., Minnella, A., Ward, J. D., Tesfaye, S., Eaton, S., Mody, C., Borra, M., Cavallo Perin, P., Giunti, S., Grassi, G., Pagano, G. F., Porta, M., Sivieri, R., Vitelli, F., Veglio, M., Papazoglou, N., Manes, G., Muggeo, M., Iagulli, M., Cacciatori, V., Cattedra di Malattie del Metabolismo, V., Irsigler, K., Abrahamian, H., Walford, S., Sinclair, J., Hughes, S., Mclelland, V., Ward, J., Roglic, G., Metelko, Z., Pepeonik, Z. R., PENNO, GIUSEPPE, MICCOLI, ROBERTO, NANNIPIERI, MONICA

المساهمون: Peeters, Stijn A., Engelen, Lian, Buijs, Jacqueline, Chaturvedi, Nish, Fuller, John H., Schalkwijk, Casper G., Stehouwer, Coen D, Karamanos, B., Kofinis, A., Petrou, K., Giorgino, F., Picca, G., Angarano, A., Null, de P. e. r. g. o. l. a. G., Laviola, L., Giorgino, R., Ionescu Tirgoviste, C., Coszma, A., Guja, C., Songini, M., Casu, A., Pedron, M., Pintus, S., Fossarello, M., Ferriss, J. B., Grealy, G., O'Keefe, D., Toeller, M., Arden, C., Rottiers, R., Tuyttens, C., Priem, H., Ebeling, P., Kylliainen, M., Koivisto, V. A., Idzior Walus, B., Sieradzki, J., Cyganek, K., Solnica, B., Lemkes, H. H. P. J., Lemkes Stuffken, J. C., Nunes Correa, J., Rogado, M. C., Gardete Correia, L., Cardoso, M. C., Silva, A., Boavida, J., Machado Sa Marques, M., Michel, G., Wirion, R., Cardillo, S., Pozza, G., Mangili, R., Asnaghi, V., Standl, E., Schaffler, B., Brand, H., Harms, A., Ben Soussan, M., Verier Mine, O., Fallas, P., Fallas, M. C., Fuller, J. H., Holloway, J., Asbury, L., Betteridge, D. J., Cathelineau, G., Bouallouche, A., Villatte Cathelineau, B., Santeusanio, F., Rosi, G., D'Alessandro, V., Cagini, C., Bottini, P., Reboldi, G. P., Navalesi, R., Penno, Giuseppe, Bandinelli, S., Miccoli, Roberto, Nannipieri, Monica, Ghirlanda, G., Saponara, C., Cotroneo, P., Manto, A., Minnella, A., Ward, J. D., Tesfaye, S., Eaton, S., Mody, C., Borra, M., Cavallo Perin, P., Giunti, S., Grassi, G., Pagano, G. F., Porta, M., Sivieri, R., Vitelli, F., Veglio, M., Papazoglou, N., Manes, G.

مصطلحات موضوعية: Albuminuria, Cardiovascular disease, Matrix metalloproteinase, Retinopathy, Tissue inhibitor of metalloproteinase, Type 1 diabete, Adult, Biomarker, Cohort Studie, Cross-Sectional Studie, Diabetes Complication, Diabetes Mellitus, Type 1, Europe, Female, Human, Male, Matrix Metalloproteinase 10, Matrix Metalloproteinase 2, Matrix Metalloproteinase 3, Middle Aged, Prospective Studie, Tissue Inhibitor of Metalloproteinase-1, Vascular Disease, Endocrinology, Diabetes and Metabolism, Cardiology and Cardiovascular Medicine

الوصف: Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25848912; volume:14; issue:1; firstpage:31; journal:CARDIOVASCULAR DIABETOLOGY; http://hdl.handle.net/11568/838374Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84925234995; http://www.cardiab.com/homeTest/

الإتاحة: https://doi.org/10.1186/s12933-015-0195-2Test
http://hdl.handle.net/11568/838374Test
http://www.cardiab.com/homeTest/