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113 results on '"Grieco, Fabio Arturo"'

1. The miRNAs miR-211-5p and miR-204-5p modulate ER stress in human beta cells

Author

Grieco, Fabio Arturo, Schiavo, Andréa Alex, Brozzi, Flora, Juan Mateu, Miguel Jonas, Bugliani, Marco, Marchetti, Piero, Eizirik, Decio L., Grieco, Fabio Arturo, Schiavo, Andréa Alex, Brozzi, Flora, Juan Mateu, Miguel Jonas, Bugliani, Marco, Marchetti, Piero, and Eizirik, Decio L.

Abstract

miRNAs are a class of small non-coding RNAs that regulate gene expression. Type 1 diabetes is an autoimmune disease characterized by insulitis (islets inflammation) and pancreatic beta cell destruction. The pro-inflammatory cytokines interleukin 1 beta (IL1B) and interferon gamma (IFNG) are released during insulitis and trigger endoplasmic reticulum (ER) stress and expression of pro-apoptotic members of the BCL2 protein family in beta cells, thus contributing to their death. The nature of miRNAs that regulate ER stress and beta cell apoptosis remains to be elucidated. We have performed a global miRNA expression profile on cytokine-treated human islets and observed a marked downregulation of miR-211-5p. By real-time PCR and Western blot analysis, we confirmed cytokine-induced changes in the expression of miR-211-5p and the closely related miR-204-5p and downstream ER stress related genes in human beta cells. Blocking of endogenous miRNA-211-5p and miR-204-5p by the same inhibitor (it is not possible to block separately these two miRs) increased human beta cell apoptosis, as measured by Hoechst/propidium Iodide staining and by determination of cleaved caspase-3 activation. Interestingly, miRs-211-5p and 204-5p regulate the expression of several ER stress markers downstream of PERK, particularly the pro-apoptotic protein DDIT3 (also known as CHOP). Blocking CHOP expression by a specific siRNA partially prevented the increased apoptosis observed following miR-211-5p/miR-204-5p inhibition. These observations identify a novel crosstalk between miRNAs, ER stress and beta cell apoptosis in early type 1 diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

2. A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction

Author

Zhong, Linlin, Tran, Tuan Anh, Baguley, Tyler T.D., Lee, Sang Jun, Henke, Adam, To, Andrew, Li, Sijia, Yu, Shan, Grieco, Fabio Arturo, Roland, Jason, Schultz, Peter, Eizirik, Decio L., Rogers, Nikki, Chartterjee, Arnab A.K., Tremblay, Matthew M.S., Shen, Weijun, Zhong, Linlin, Tran, Tuan Anh, Baguley, Tyler T.D., Lee, Sang Jun, Henke, Adam, To, Andrew, Li, Sijia, Yu, Shan, Grieco, Fabio Arturo, Roland, Jason, Schultz, Peter, Eizirik, Decio L., Rogers, Nikki, Chartterjee, Arnab A.K., Tremblay, Matthew M.S., and Shen, Weijun

Abstract

Background and Purpose: Beta cell apoptosis is a major feature of type 1 diabetes, and pro-inflammatory cytokines are key drivers of the deterioration of beta cell mass through induction of apoptosis. Mitochondrial stress plays a critical role in mediating apoptosis by releasing cytochrome C into the cytoplasm, directly activating caspase-9 and its downstream signalling cascade. We aimed to identify new compounds that protect beta cells from cytokine-induced activation of the intrinsic (mitochondrial) pathway of apoptosis. Experimental Approach: Diabetogenic media, composed of IL-1β, IFN-γ and high glucose, were used to induce mitochondrial stress in rat insulin-producing INS1E cells, and a high-content image-based screen of small molecule modulators of Casp9 pathway was performed. Key Results: A novel small molecule, ATV399, was identified from a high-content image-based screen for compounds that inhibit cleaved caspase-9 activation and subsequent beta cell apoptosis induced by a combination of IL-1β, IFN-γ and high glucose, which together mimic the pathogenic diabetic milieu. Through medicinal chemistry optimization, potency was markedly improved (6–30 fold), with reduced inhibitory effects on CYP3A4. Improved analogues, such as CAT639, improved beta cell viability and insulin secretion in cytokine-treated rat insulin-producing INS1E cells and primary dispersed islet cells. Mechanistically, CAT639 reduced the production of NO by allosterically inhibiting dimerization of inducible NOS (iNOS) without affecting its mRNA levels. Conclusion and Implications: Taken together, these studies demonstrate a successful phenotypic screening campaign resulting in identification of an inhibitor of iNOS dimerization that protects beta cell viability and function through modulation of mitochondrial stress induced by cytokines., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

3. Protective role of complement C3 against cytokine-mediated β-cell apoptosis

Author

Dos Santos, Reinaldo Sousa, Marroquí, Laura, Grieco, Fabio Arturo, Marselli, Lorella, Suleiman, Mara, Henz, Stefan S.R., Marchetti, Piero, Wernersson, Rasmus, Eizirik, Decio L., Dos Santos, Reinaldo Sousa, Marroquí, Laura, Grieco, Fabio Arturo, Marselli, Lorella, Suleiman, Mara, Henz, Stefan S.R., Marchetti, Piero, Wernersson, Rasmus, and Eizirik, Decio L.

Abstract

Type 1 diabetes is a chronic autoimmune disease characterized by pancreatic islet inflammation and β-cell destruction by proinflammatory cytokines and other mediators. Based on RNA sequencing and protein-protein interaction analyses of human islets exposed to proinflammatory cytokines, we identified complement C3 as a hub for some of the effects of cytokines. The proinflammatory cytokines interleukin-1b plus interferon-g increase C3 expression in rodent and human pancreatic β-cells, and C3 is detected by histology in and around the islets of diabetic patients. Surprisingly, C3 silencing exacerbates apoptosis under both basal condition and following exposure to cytokines, and it increases chemokine expression upon cytokine treatment. C3 exerts its prosurvival effects via AKT activation and c-Jun N-terminal kinase inhibition. Exogenously added C3 also protects against cytokine-induced β-cell death and partially rescues the deleterious effects of inhibition of endogenous C3. These data suggest that locally produced C3 is an important prosurvival mechanism in pancreatic β-cells under a proinflammatory assault., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

4. Pancreatic β-cell protection from inflammatory stress by the endoplasmic reticulum proteins thrombospondin 1 and mesencephalic astrocyte-derived neutrotrophic factor (MANF)

Author

Andrade Da Cunha, Daniel, Marchetti, Piero, Eizirik, Decio L., Cnop, Miriam, Cito, Monia, Grieco, Fabio Arturo, Cosentino, Cristina, Danilova, Tatiana, Ladrière, Laurence, Lindahl, Maria, Domanskyi, Andrii, Bugliani, Marco, Andrade Da Cunha, Daniel, Marchetti, Piero, Eizirik, Decio L., Cnop, Miriam, Cito, Monia, Grieco, Fabio Arturo, Cosentino, Cristina, Danilova, Tatiana, Ladrière, Laurence, Lindahl, Maria, Domanskyi, Andrii, and Bugliani, Marco

Abstract

Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular mechanisms underlying pancreatic β-cell demise in type 1 diabetes. Thrombospondin 1 (THBS1) was recently shown to promote β-cell survival during lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat, mouse, andhumanβ-cells exposed to cytokines or thapsigargininduced ER stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic astrocyte-derived neutrotrophic factor (MANF) in β-cells and thereby prevents the BH3-only protein BIM (BCL2-interacting mediator of cell death)-dependent triggering of the mitochondrial pathway of apoptosis. Prolonged exposure ofβ-cells to cytokines or thapsigargin leads to THBS1 and MANF degradation and loss of this prosurvival mechanism. Approaches that sustain intracellular THBS1 and MANF expression in β-cells should be explored as a cytoprotective strategy in type 1 diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

5. Tolerogenic insulin peptide therapy precipitates type 1 diabetes

Author

Bergman, Marie Louise, Lopes-Carvalho, Thiago, Martins, Ana Catarina, Grieco, Fabio Arturo, Eizirik, Decio L., Demengeot, Jocelyne, Bergman, Marie Louise, Lopes-Carvalho, Thiago, Martins, Ana Catarina, Grieco, Fabio Arturo, Eizirik, Decio L., and Demengeot, Jocelyne

Abstract

Daniel et al. (https://doi.org/10.1084/jem.20110574) have previously published in JEM a study on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Our study now challenges these results and shows that osmotic pump delivery of the modified insulin peptide R22E did not prevent hyperglycemia, accelerated disease onset, increased its incidence, and worsened insulitis., SCOPUS: le.j, info:eu-repo/semantics/published

Published
2017

6. MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic Beta Cells

Author

Grieco, Fabio Arturo, Sebastiani, Guido, Juan Mateu, Miguel Jonas, Villate, Olatz, Marroquí, Laura, Ladrière, Laurence, Tugay, Kenia, Regazzi, Romano, Bugliani, Marco, Marchetti, Piero, Dotta, Francesco, Eizirik, Decio L., Grieco, Fabio Arturo, Sebastiani, Guido, Juan Mateu, Miguel Jonas, Villate, Olatz, Marroquí, Laura, Ladrière, Laurence, Tugay, Kenia, Regazzi, Romano, Bugliani, Marco, Marchetti, Piero, Dotta, Francesco, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/published

Published
2017

7. SRp55 Regulates a Splicing Network that Controls Human Pancreatic Beta Cell Function and Survival.

Author

Juan-Mateu, Jonàs, Alvelos, Maria Inês, Turatsinze, Jean Valéry, Villate, Olatz, Lizarraga-Mollinedo, Esther, Grieco, Fabio Arturo, Marroquí, Laura, Bugliani, Marco, Marchetti, Piero, Eizirik, Decio L., Juan-Mateu, Jonàs, Alvelos, Maria Inês, Turatsinze, Jean Valéry, Villate, Olatz, Lizarraga-Mollinedo, Esther, Grieco, Fabio Arturo, Marroquí, Laura, Bugliani, Marco, Marchetti, Piero, and Eizirik, Decio L.

Abstract

Progressive failure of insulin-producing beta cells is the central event leading to diabetes, but the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

8. Ubiquitin D Regulates IRE1alpha/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells.

Author

Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Juusola, Matilda, Balhuizen, Alexander, Lievens, Sam, Gysemans, Conny, Bugliani, Marco, Mathieu, Chantal, Marchetti, Piero, Tavernier, Jan, Eizirik, Decio, Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Juusola, Matilda, Balhuizen, Alexander, Lievens, Sam, Gysemans, Conny, Bugliani, Marco, Mathieu, Chantal, Marchetti, Piero, Tavernier, Jan, and Eizirik, Decio

Abstract

Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1 diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). It remains to be determined what causes the transition from "physiological" to "apoptotic" UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1α is critical for this transition. IRE1α activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1α-interacting protein ubiquitin D (UBD) on the regulation of IRE1α and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1α interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown of UBD in human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1α activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1β and interferon (IFN)-γ in rat and human pancreatic beta cells, and it is also up-regulated in beta cells of inflamed islets from non-obese diabetic mice. UBD interacts with IRE1α in human and rodent beta cells, modulating IRE1α-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1α/JNK pro-apoptotic pathway in cytokine-exposed beta cells., info:eu-repo/semantics/published

Published
2016

9. Regulation of pancreatic beta cell function and survival by alternative splicing: the role of the splicing factor SRp55.

Author

Juan Mateu, Miguel Jonas, De Oliveira Alvelos, Maria, Turatsinze, Jean Valéry, Villate, Olatz, Grieco, Fabio Arturo, Marroquí, Laura, Eizirik, Decio L., Juan Mateu, Miguel Jonas, De Oliveira Alvelos, Maria, Turatsinze, Jean Valéry, Villate, Olatz, Grieco, Fabio Arturo, Marroquí, Laura, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/published

Published
2016

10. SRp55 regulates splicing networks controlling key pathways for human beta cell function and survival.

Author

HIRI Annual Investigator meeting. 15 March 2016, Washington USA. (Poster), Juan Mateu, Miguel Jonas, De Oliveira Alvelos, Maria, Turatsinze, Jean Valéry, Villate, Olatz, Grieco, Fabio Arturo, Marroquí, Laura, Eizirik, Decio, HIRI Annual Investigator meeting. 15 March 2016, Washington USA. (Poster), Juan Mateu, Miguel Jonas, De Oliveira Alvelos, Maria, Turatsinze, Jean Valéry, Villate, Olatz, Grieco, Fabio Arturo, Marroquí, Laura, and Eizirik, Decio

Abstract

info:eu-repo/semantics/nonPublished

Published
2016

11. The Achilles heel of pancreatic beta cells in Type 1 Diabetes ?

Author

DAMPs, Référence Injury Perception and Immunity Across the Tree of Life (6th-11th November 2016: Guanajuata, Mexico), Marroquí, Laura, Lopes, Miguel, Sousa Do Santos, Reinaldo, Grieco, Fabio Arturo, Roivainen, Merja, Richardson, S J, Morgan, N G, Eizirik, Decio L., Op De Beeck, Anne, DAMPs, Référence Injury Perception and Immunity Across the Tree of Life (6th-11th November 2016: Guanajuata, Mexico), Marroquí, Laura, Lopes, Miguel, Sousa Do Santos, Reinaldo, Grieco, Fabio Arturo, Roivainen, Merja, Richardson, S J, Morgan, N G, Eizirik, Decio L., and Op De Beeck, Anne

Abstract

info:eu-repo/semantics/nonPublished

Published
2016

12. A combined “omics” approach identifies NMI as a novel cytokine-induced regulator of IRE1α and JNK in pancreatic beta cells.

Author

1st National Diabetes Excellence Summit. 25 April 2015, Bruxelles, Belgium. (Poster), Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, Eizirik, Decio L., 1st National Diabetes Excellence Summit. 25 April 2015, Bruxelles, Belgium. (Poster), Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2015

13. Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms

Author

Brozzi, Flora, Nardelli, Tarlliza R, Lopes, Miguel, Millard, Isabelle, Barthson, Jenny, Igoillo Esteve, Mariana, Grieco, Fabio Arturo, Villate, Olatz, Oliveira, Joana Moitinho Oitinho J.M., Casimir, Marina, Bugliani, Marco, Engin, Feyza, Hotamisligil, Gökhan S., Marchetti, Piero, Eizirik, Decio L., Brozzi, Flora, Nardelli, Tarlliza R, Lopes, Miguel, Millard, Isabelle, Barthson, Jenny, Igoillo Esteve, Mariana, Grieco, Fabio Arturo, Villate, Olatz, Oliveira, Joana Moitinho Oitinho J.M., Casimir, Marina, Bugliani, Marco, Engin, Feyza, Hotamisligil, Gökhan S., Marchetti, Piero, and Eizirik, Decio L.

Abstract

Aims/hypothesis: Proinflammatory cytokines contribute to beta cell damage in type 1 diabetes in part through activation of endoplasmic reticulum (ER) stress. In rat beta cells, cytokine-induced ER stress involves NO production and consequent inhibition of the ER Ca2+ transporting ATPase sarco/endoplasmic reticulum Ca2+ pump 2 (SERCA2B). However, the mechanisms by which cytokines induce ER stress and apoptosis in mouse and human pancreatic beta cells remain unclear. The purpose of this study is to elucidate the role of ER stress on cytokine-induced beta cell apoptosis in these three species and thus solve ongoing controversies in the field. Methods: Rat and mouse insulin-producing cells, human pancreatic islets and human EndoC-βH1 cells were exposed to the cytokines IL-1β, TNF-α and IFN-γ, with or without NO inhibition. A global comparison of cytokine-modulated gene expression in human, mouse and rat beta cells was also performed. The chemical chaperone tauroursodeoxycholic acid (TUDCA) and suppression of C/EBP homologous protein (CHOP) were used to assess the role of ER stress in cytokine-induced apoptosis of human beta cells. Results: NO plays a key role in cytokine-induced ER stress in rat islets, but not in mouse or human islets. Bioinformatics analysis indicated greater similarity between human and mouse than between human and rat global gene expression after cytokine exposure. The chemical chaperone TUDCA and suppression of CHOP or c-Jun N-terminal kinase (JNK) protected human beta cells against cytokine-induced apoptosis. Conclusions/interpretation: These observations clarify previous results that were discrepant owing to the use of islets from different species, and confirm that cytokine-induced ER stress contributes to human beta cell death, at least in part via JNK activation., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

14. Pancreatic alpha-cells are resistant to metabolic stress-induced apoptosis in Type 2 Diabetes

Author

Marroquí, Laura, Eizirik, Decio L., Masini, Matilde, Merino, Beatriz, Grieco, Fabio Arturo, Millard, Isabelle, Dubois, Christine, Quesada, Iván, Marchetti, Piero, Cnop, Miriam, Marroquí, Laura, Eizirik, Decio L., Masini, Matilde, Merino, Beatriz, Grieco, Fabio Arturo, Millard, Isabelle, Dubois, Christine, Quesada, Iván, Marchetti, Piero, and Cnop, Miriam

Abstract

Pancreatic α cells are exposed to metabolic stress during the evolution of type 2 diabetes (T2D), but it remains unclear whether this affects their survival. We used electron microscopy to search for markers of apoptosis and endoplasmic reticulum (ER) stress in α and β cells in islets from T2D or non-diabetic individuals. There was a significant increase in apoptotic β cells (from 0.4% in control to 6.0% in T2D), but no α cell apoptosis. We observed, however, similar ER stress in α and β cells from T2D patients. Human islets or fluorescence-activated cell sorting (FACS)-purified rat β and α cells exposed in vitro to the saturated free fatty acid palmitate showed a similar response as the T2D islets, i.e. both cell types showed signs of ER stress but only β cells progressed to apoptosis. Mechanistic experiments indicate that this α cell resistance to palmitate-induced apoptosis is explained, at least in part, by abundant expression of the anti-apoptotic protein Bcl2l1 (also known as Bcl-xL)., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

15. Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic alpha and bêta cells.

Author

Marroquí, Laura, Lopes, Miguel, Dos Santos, Reinaldo Sousa, Grieco, Fabio Arturo, Roivainen, Merja, Richardson, S J, Morgan, N G, Eizirik, Decio L., Op De Beeck, Anne, Marroquí, Laura, Lopes, Miguel, Dos Santos, Reinaldo Sousa, Grieco, Fabio Arturo, Roivainen, Merja, Richardson, S J, Morgan, N G, Eizirik, Decio L., and Op De Beeck, Anne

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighbouring α cells are preserved. Viral infections by Coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D., info:eu-repo/semantics/published

Published
2015

16. TYK2, a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic bêta-Cells.

Author

Marroquí, Laura, Dos Santos, Reinaldo Sousa, Fløyel, Tina, Grieco, Fabio Arturo, Santin Gomez, Izortze, Op De Beeck, Anne, Marselli, Lorella, Marchetti, Piero, Pociot, Flemming Michael, Eizirik, Decio L., Marroquí, Laura, Dos Santos, Reinaldo Sousa, Fløyel, Tina, Grieco, Fabio Arturo, Santin Gomez, Izortze, Op De Beeck, Anne, Marselli, Lorella, Marchetti, Piero, Pociot, Flemming Michael, and Eizirik, Decio L.

Abstract

Pancreatic β-cells are destroyed by an autoimmune attack in type 1 diabetes. Linkage and genome-wide association studies point to >50 loci that are associated with the disease in the human genome. Pathway analysis of candidate genes expressed in human islets identified a central role for interferon (IFN)-regulated pathways and tyrosine kinase 2 (TYK2). Polymorphisms in the TYK2 gene predicted to decrease function are associated with a decreased risk of developing type 1 diabetes. We presently evaluated whether TYK2 plays a role in human pancreatic β-cell apoptosis and production of proinflammatory mediators. TYK2-silenced human β-cells exposed to polyinosinic-polycitidilic acid (PIC) (a mimick of double-stranded RNA produced during viral infection) showed less type I IFN pathway activation and lower production of IFNα and CXCL10. These cells also had decreased expression of major histocompatibility complex (MHC) class I proteins, a hallmark of early β-cell inflammation in type 1 diabetes. Importantly, TYK2 inhibition prevented PIC-induced β-cell apoptosis via the mitochondrial pathway of cell death. The present findings suggest that TYK2 regulates apoptotic and proinflammatory pathways in pancreatic β-cells via modulation of IFNα signaling, subsequent increase in MHC class I protein, and modulation of chemokines such as CXCL10 that are important for recruitment of T cells to the islets., info:eu-repo/semantics/published

Published
2015

17. Insulinoma localization by glucagon-like peptide-1 receptor imaging after 18 years of hypoglycemia

Author

Kyrilli, Aglaia, Igoillo Esteve, Mariana, Fery, Françoise, Grieco, Fabio Arturo, Eisendrath, Pierre, Blocklet, Didier, Goldman, Serge, Henquin, Jean Claude, Gotthardt, Martin, Cnop, Miriam, Kyrilli, Aglaia, Igoillo Esteve, Mariana, Fery, Françoise, Grieco, Fabio Arturo, Eisendrath, Pierre, Blocklet, Didier, Goldman, Serge, Henquin, Jean Claude, Gotthardt, Martin, and Cnop, Miriam

Abstract

info:eu-repo/semantics/published

Published
2015

18. Insulinoma localization by glucagon-like peptide-1 receptor imaging after 18 years of hypoglycemia

Author

Kyrilli, Aglaia, Igoillo Esteve, Mariana, Fery, Françoise, Grieco, Fabio Arturo, Eisendrath, Pierre, Blocklet, Didier, Goldman, Serge, Henquin, Jean Claude, Gotthardt, Martin, Cnop, Miriam, Kyrilli, Aglaia, Igoillo Esteve, Mariana, Fery, Françoise, Grieco, Fabio Arturo, Eisendrath, Pierre, Blocklet, Didier, Goldman, Serge, Henquin, Jean Claude, Gotthardt, Martin, and Cnop, Miriam

Abstract

info:eu-repo/semantics/published

Published
2015

19. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells.

Author

1st National Diabetes Excellence Summit. 25 April 2015, Bruxelles, Belgium. (Poster), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, De Araujo Nogueira, Tatiane, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, Eizirik, Decio L., 1st National Diabetes Excellence Summit. 25 April 2015, Bruxelles, Belgium. (Poster), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, De Araujo Nogueira, Tatiane, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2015

20. TYK2, a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic Beta Cells.

Author

Marroquí, Laura, Dos Santos, Reinaldo Sousa, Floyel, T, Grieco, Fabio Arturo, Santin Gomez, Izortze, Op de Beek, A, Marselli, L, Marchetti, Piero, Pociot, Flemming, Eizirik, Decio L., Marroquí, Laura, Dos Santos, Reinaldo Sousa, Floyel, T, Grieco, Fabio Arturo, Santin Gomez, Izortze, Op de Beek, A, Marselli, L, Marchetti, Piero, Pociot, Flemming, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/published

Published
2015

21. A combined “omics” approach identifies NMI as a novel cytokine-induced regulator of IRE1α and JNK in pancreatic beta cells

Author

EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Poster)), Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, Eizirik, Decio L., EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Poster)), Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2014

22. A combined omics approach identifies NMI as a novel cytokine-induced regulator of IRE1α and JNK in pancreatic beta cells.

Author

Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Nardelli, Tarlliza R, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, Eizirik, Decio L., Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Nardelli, Tarlliza R, Lievens, Sam, Gysemans, Conny, Marselli, Lorella, Marchetti, Piero, Mathieu, Chantal, Tavernier, Jan, and Eizirik, Decio L.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease with a strong inflammatory component. The cytokines interleukin-1β and interferon-γ contribute to beta cell apoptosis in T1D. These cytokines induce endoplasmic reticulum stress and the unfolded protein response (UPR), contributing to loss of beta cells. IRE1α, one of the UPR mediators, triggers insulin degradation and inflammation in beta cells and is critical for the transition from ″physiological″ to ″pathological″ UPR. The mechanisms regulating IRE1α activation, and its signalling for beta cell ″adaptation″, ″stress response″ or ″apoptosis″ remain to be clarified. To address these questions we combined MAPPIT (MAmmalian Protein-Protein Interaction Trap)-based IRE1α interactome and functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines to identify novel cytokine-induced regulators of IRE1α. Based on this approach, we identified N-myc interactor (NMI) as an IRE1α-interacting/modulator protein in rodent and human pancreatic beta cells. An increased expression of NMI was detected in islets from non-obese diabetic (NOD) mice with insulitis, and in rodent or human beta cells exposed in vitro to the pro-inflammatory cytokines interleukin-1β and interferon-γ. Detailed mechanistic studies demonstrated that NMI negatively modulates IRE1α-dependent activation of JNK and apoptosis in rodent and human pancreatic beta cells. In conclusion, by using a combined omics approach, we identified NMI induction as a novel negative feedback mechanism that decreases IRE1α-dependent activation of JNK and apoptosis in cytokine-exposed beta cells., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

23. IL-17A increases the expression of proinflammatory chemokines in human pancreatic islets.

Author

Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Villate, Olatz, Marselli, Lorella, Rondas, Dieter, Korf, Hannelie, Overbergh, Lutgart, Dotta, Francesco, Marchetti, Piero, Mathieu, Chantal, Eizirik, Decio L., Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Villate, Olatz, Marselli, Lorella, Rondas, Dieter, Korf, Hannelie, Overbergh, Lutgart, Dotta, Francesco, Marchetti, Piero, Mathieu, Chantal, and Eizirik, Decio L.

Abstract

Cytotoxic T cells and macrophages contribute to beta cell destruction in type 1 diabetes at least in part through the production of cytokines such as IL-1β, IFN-γ and TNF-α. We have recently shown the IL-17 pathway to be activated in circulating T cells and pancreatic islets of type 1 diabetes patients. Here, we studied whether IL-17A upregulates the production of chemokines by human pancreatic islets, thus contributing to the build-up of insulitis., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

24. Nova1 is a master regulator of alternative splicing in pancreatic beta cells.

Author

Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Nardelli, Tarlliza R, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, Eizirik, Decio L., Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Nardelli, Tarlliza R, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, and Eizirik, Decio L.

Abstract

Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signaling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

25. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells

Author

EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Oral Presentation)), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, Eizirik, Decio L., EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Oral Presentation)), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2014

26. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells

Author

EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Oral Presentation)), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, Eizirik, Decio L., EASD 2014, 50th Annual Meeting of the European Association for the Study of Diabetes (15 - 19 September 2014: Vienna, Austria. (Oral Presentation)), Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2014

27. Nova1 is a master regulator of alternative splicing in pancreatic beta cells.

Author

Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Nardelli, Tarlliza R, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, Eizirik, Decio L., Villate, Olatz, Turatsinze, Jean Valéry, Mascali, Loriana, Grieco, Fabio Arturo, Nogueira, Tatiane C, Andrade Da Cunha, Daniel, Nardelli, Tarlliza R, Sammeth, Michael, Salunkhe, Vishal VA, Esguerra, Jonathan JL, Eliasson, Lena, Marselli, Lorella, Marchetti, Piero, and Eizirik, Decio L.

Abstract

Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signaling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

28. Coxsackie-Virus and Insulitis: Diabetes and Virus

Author

Galleri, Letizia, Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Vendrame, Francesco, Dotta, Francesco, Galleri, Letizia, Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Vendrame, Francesco, and Dotta, Francesco

Abstract

info:eu-repo/semantics/published, 1

Published
2013

29. IL-17 increases the expression and release of pro-inflammatory chemokines by human pancreatic islets

Author

EASD 2013, 49th Annual Meeting of the European Association for the Study of Diabetes (23 - 27 September: Barcelona, Spain. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Rondas, Dieter, Overbergh, Lutgart, Dotta, Francesco, Mathieu, Chantal, Marchetti, Piero, Eizirik, Decio L., EASD 2013, 49th Annual Meeting of the European Association for the Study of Diabetes (23 - 27 September: Barcelona, Spain. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Rondas, Dieter, Overbergh, Lutgart, Dotta, Francesco, Mathieu, Chantal, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

30. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells.

Author

Benelux Bioinformatics Conference 2013 (09-10 December 2013: Brussels, Belgium. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, Eizirik, Decio L., Benelux Bioinformatics Conference 2013 (09-10 December 2013: Brussels, Belgium. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

31. Beta cell expression of enteroviral receptor CAR and islets inflammation in human type 1 diabetes

Author

nPOD 2013, 5th Annual Meeting of the Network for Pancreatic Organ Donors with Diabetes (10-13 February 2013: Atlantic Beach, Florida. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Mancarella, Francesca, Dotta, Francesco, nPOD 2013, 5th Annual Meeting of the Network for Pancreatic Organ Donors with Diabetes (10-13 February 2013: Atlantic Beach, Florida. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Mancarella, Francesca, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

32. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells.

Author

23th Islet Study Group Symposium (27 - 29 September 2013: Sitges, Barcelona, Spain. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, Eizirik, Decio L., 23th Islet Study Group Symposium (27 - 29 September 2013: Sitges, Barcelona, Spain. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

33. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells.

Author

Benelux Bioinformatics Conference 2013 (09-10 December 2013: Brussels, Belgium. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, Eizirik, Decio L., Benelux Bioinformatics Conference 2013 (09-10 December 2013: Brussels, Belgium. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

34. IL-17 increases the expression and release of pro-inflammatory chemokines by human pancreatic islets

Author

EASD 2013, 49th Annual Meeting of the European Association for the Study of Diabetes (23 - 27 September: Barcelona, Spain. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Rondas, Dieter, Overbergh, Lutgart, Dotta, Francesco, Mathieu, Chantal, Marchetti, Piero, Eizirik, Decio L., EASD 2013, 49th Annual Meeting of the European Association for the Study of Diabetes (23 - 27 September: Barcelona, Spain. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Rondas, Dieter, Overbergh, Lutgart, Dotta, Francesco, Mathieu, Chantal, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

35. Coxsackie-Virus and Insulitis: Diabetes and Virus

Author

Galleri, Letizia, Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Vendrame, Francesco, Dotta, Francesco, Galleri, Letizia, Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Vendrame, Francesco, and Dotta, Francesco

Abstract

info:eu-repo/semantics/published, 1

Published
2013

36. Beta cell expression of enteroviral receptor CAR and islets inflammation in human type 1 diabetes

Author

nPOD 2013, 5th Annual Meeting of the Network for Pancreatic Organ Donors with Diabetes (10-13 February 2013: Atlantic Beach, Florida. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Mancarella, Francesca, Dotta, Francesco, nPOD 2013, 5th Annual Meeting of the Network for Pancreatic Organ Donors with Diabetes (10-13 February 2013: Atlantic Beach, Florida. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Mancarella, Francesca, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

37. RNA-sequencing identifies Nova1 as a major splicing regulator in pancreatic beta cells.

Author

23th Islet Study Group Symposium (27 - 29 September 2013: Sitges, Barcelona, Spain. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, Eizirik, Decio L., 23th Islet Study Group Symposium (27 - 29 September 2013: Sitges, Barcelona, Spain. (Poster)), Villate, Olatz, Turatsinze, Jean Valéry, Nogueira, Tatiane C, Grieco, Fabio Arturo, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2013

38. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice

Author

Takiishi, Tatiana, Korf, Hannelie, Van Belle, Tom L, Robert, Sofie, Grieco, Fabio Arturo, Caluwaerts, Silvia, Galleri, Letizia, Spagnuolo, Isabella, Steidler, Lothar, Van Huynegem, Karolien, Demetter, Pieter, Wasserfall, Clive, Atkinson, Mark, Dotta, Francesco, Rottiers, Pieter, Gysemans, Conny, Mathieu, Chantal, Takiishi, Tatiana, Korf, Hannelie, Van Belle, Tom L, Robert, Sofie, Grieco, Fabio Arturo, Caluwaerts, Silvia, Galleri, Letizia, Spagnuolo, Isabella, Steidler, Lothar, Van Huynegem, Karolien, Demetter, Pieter, Wasserfall, Clive, Atkinson, Mark, Dotta, Francesco, Rottiers, Pieter, Gysemans, Conny, and Mathieu, Chantal

Abstract

SCOPUS: no.j, info:eu-repo/semantics/published

Published
2013

39. Beta cell expression of enteroviral receptor CAR and islet inflammation in human type 1 diabetes

Author

EASD 2012, 48th Annual Meeting of the European Association for the Study of Diabetes (1 - 5 October 2012: Berlin, Germany. (Poster)), Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Grieco, Fabio Arturo, Dotta, Francesco, EASD 2012, 48th Annual Meeting of the European Association for the Study of Diabetes (1 - 5 October 2012: Berlin, Germany. (Poster)), Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Grieco, Fabio Arturo, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

40. A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets.

Author

Marchetti, Piero, Lupi, R., Bugliani, M, Kirkpatrick, C L, Sebastiani, Guido, Grieco, Fabio Arturo, Del Guerra, Silvia, D'Aleo, Valentina, Piro, Salvatore, Marselli, L, Boggi, U, Filipponi, F, Tinti, Laura, Salvini, Laura, Wollheim, C B, Purrello, Francesco, Dotta, F, Marchetti, Piero, Lupi, R., Bugliani, M, Kirkpatrick, C L, Sebastiani, Guido, Grieco, Fabio Arturo, Del Guerra, Silvia, D'Aleo, Valentina, Piro, Salvatore, Marselli, L, Boggi, U, Filipponi, F, Tinti, Laura, Salvini, Laura, Wollheim, C B, Purrello, Francesco, and Dotta, F

Abstract

Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients., info:eu-repo/semantics/published

Published
2012

41. Viral infections and diabetes.

Author

Galleri, Letizia, Sebastiani, Guido, Vendrame, Francesco, Grieco, Fabio Arturo, Spagnuolo, Isabella, Dotta, Francesco, Galleri, Letizia, Sebastiani, Guido, Vendrame, Francesco, Grieco, Fabio Arturo, Spagnuolo, Isabella, and Dotta, Francesco

Abstract

Type 1 diabetes mellitus (T1DM) is a multi-factorial autoimmune disease determined by the interaction of genetic, environmental and immunologic factors. One of the environmental risk factors identified by a series of independent studies is represented by viral infection, with strong evidence showing that viruses can indeed infect pancreatic beta cells with consequent effects ranging from functional damage to cell death. In this chapter we review the data obtained both in man and in experimental animal models in support of the potential participation of viral infections to Type 1 diabetes pathogenesis, with a particular emphasis on virus-triggered islet inflammation, beta-cell dysfunction and autoimmunity., info:eu-repo/semantics/published

Published
2012

42. IL-17 increases the expression and release of pro-inflammatory chemokines by human pancreatic islets

Author

ISG 2012, 22th Islet Study Group Symposium (5 - 7 October 2012: Rostock, Germany. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Overbergh, Lutgart, Mathieu, Chantal, Dotta, Francesco, Marchetti, Piero, Eizirik, Decio L., ISG 2012, 22th Islet Study Group Symposium (5 - 7 October 2012: Rostock, Germany. (Poster)), Grieco, Fabio Arturo, Moore, Fabrice, Vigneron, François, Santin Gomez, Izortze, Marselli, Lorella, Overbergh, Lutgart, Mathieu, Chantal, Dotta, Francesco, Marchetti, Piero, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

43. USP18 is a key regulator of the interferon-driven gene network modulating pancreatic beta cell inframmation and apoptosis

Author

ISG 2012, 22th Islet Study Group Symposium (5 - 7 October 2012: Rostock, Germany (Poster)), Santin Gomez, Izortze, Moore, Fabrice, Grieco, Fabio Arturo, Marchetti, Piero, Brancolini, C, Eizirik, Decio L., ISG 2012, 22th Islet Study Group Symposium (5 - 7 October 2012: Rostock, Germany (Poster)), Santin Gomez, Izortze, Moore, Fabrice, Grieco, Fabio Arturo, Marchetti, Piero, Brancolini, C, and Eizirik, Decio L.

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

44. Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function.

Author

Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Patti, Aurora, Dotta, F, Grieco, Fabio Arturo, Sebastiani, Guido, Spagnuolo, Isabella, Patti, Aurora, and Dotta, F

Abstract

Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals. Epidemiological evidence has also documented the constant rise in the incidence of T1DM worldwide, with viral infections representing one of the candidate environmental risk factors identified by several independent studies. In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that viruses can infect pancreatic beta cells with consequent effects ranging from functional damage to cell death., FLWIN, info:eu-repo/semantics/published

Published
2012

45. Caratterizzazione del profilo di espressione dei microRNA circolanti nel siero di pazienti affetti da diabete mellito di tipo 1

Author

SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Poster)), Sebastiani, Guido, Spagnuolo, Isabella, Grieco, Fabio Arturo, Patti, Aurora, Cataldo, Dorica, Tiberti, Claudio, Dotta, Francesco, SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Poster)), Sebastiani, Guido, Spagnuolo, Isabella, Grieco, Fabio Arturo, Patti, Aurora, Cataldo, Dorica, Tiberti, Claudio, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

46. Dimostrazione dei linfociti T CD8 autoreattivi contro autoantigeni insulari nell’insulite dei pazienti con diabete tipo 1. SID 2012, 24th National Conference, Società Italiana Diabetologia

Author

SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Oral presentation)), Patti, Aurora, Spagnuolo, Isabella, Grieco, Fabio Arturo, Sebastiani, Guido, Roep, Bart, Dotta, Francesco, SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Oral presentation)), Patti, Aurora, Spagnuolo, Isabella, Grieco, Fabio Arturo, Sebastiani, Guido, Roep, Bart, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

47. Regressione del diabete autoimmune tramite ripristino della tolerranza antigene-specifica usando il Lactoccoccus Lactis geneticamente modificato.

Author

SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Oral presentation)), Spagnuolo, Isabella, Grieco, Fabio Arturo, Patti, Aurora, Sebastiani, Guido, Mathieu, Chantal, Dotta, Francesco, SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Oral presentation)), Spagnuolo, Isabella, Grieco, Fabio Arturo, Patti, Aurora, Sebastiani, Guido, Mathieu, Chantal, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

48. Specific microRNAs expression fingerprint in serum of Type 1 Diabetic Patient.

Author

IDS 2012, 12th International Conference on the Immunology of Diabetes Society (15-19 June 2012: Victoria, Canada. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Ferretti, Elisabetta, Tiberti, Claudio, Dotta, Francesco, IDS 2012, 12th International Conference on the Immunology of Diabetes Society (15-19 June 2012: Victoria, Canada. (Poster)), Spagnuolo, Isabella, Sebastiani, Guido, Patti, Aurora, Grieco, Fabio Arturo, Ferretti, Elisabetta, Tiberti, Claudio, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

49. Cellule masenchimali derivate da isole pancreatiche umane di pazienti con diabete di tipo 2 presentano ridotte capacità proliferative e differenziative

Author

SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Poster)), Grieco, Fabio Arturo, Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Bugliani, Marco, Marselli, Lorella, Marchetti, Piero, Dotta, Francesco, SID 2012, 24th National Conference, Società Italiana Diabetologia (23 – 26 May 2012: Torino, Italy. (Poster)), Grieco, Fabio Arturo, Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Bugliani, Marco, Marselli, Lorella, Marchetti, Piero, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

50. Defective proliferative and differentiation proprierties of human pancreatic islets derived mesenchymal cells from type 2 diabetic donors

Author

EASD 2012, 48th Annual Meeting of the European Association for the Study of Diabetes (1 - 5 October 2012: Berlin, Germany. (Poster)), Grieco, Fabio Arturo, Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Bugliani, Marco, Marselli, Lorella, Marchetti, Piero, Dotta, Francesco, EASD 2012, 48th Annual Meeting of the European Association for the Study of Diabetes (1 - 5 October 2012: Berlin, Germany. (Poster)), Grieco, Fabio Arturo, Spagnuolo, Isabella, Patti, Aurora, Sebastiani, Guido, Bugliani, Marco, Marselli, Lorella, Marchetti, Piero, and Dotta, Francesco

Abstract

info:eu-repo/semantics/nonPublished

Published
2012

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