المؤلفون: Cecile Jacovetti, Chris Donnelly, Véronique Menoud, Mara Suleiman, Cristina Cosentino, Jonathan Sobel, Kejing Wu, Karim Bouzakri, Piero Marchetti, Claudiane Guay, Bengt Kayser, Romano Regazzi

المصدر: Molecular Metabolism, Vol 84, Iss , Pp 101955- (2024)

مصطلحات موضوعية: Insulin secretion, Mitochondrial OXPHOS, Mitochondrial tRNA-derived fragments, Internal medicine, RC31-1245

الوصف: Objective: The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-LeuTAA) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-LeuTAA, on mitochondrial metabolism and pancreatic islet functions. Methods: We used antisense oligonucleotides to reduce mt-tRF-LeuTAA levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-LeuTAA inhibition. Additionally, we employed pull-down assays followed by mass spectrometry to identify direct interactors of the fragment. Finally, we characterized the impact of mt-tRF-LeuTAA silencing on the coupling between mitochondrial metabolism and insulin secretion using high-resolution respirometry and insulin secretion assays. Results: Our study unveils a modulation of mt-tRF-LeuTAA levels in pancreatic islets in different Type 2 diabetes models and in response to changes in nutritional status. The level of the fragment is finely tuned by the mechanistic target of rapamycin complex 1. Located within mitochondria, mt-tRF-LeuTAA interacts with core subunits and assembly factors of respiratory complexes of the electron transfer system. Silencing of mt-tRF-LeuTAA in islet cells limits the inner mitochondrial membrane potential and impairs mitochondrial oxidative phosphorylation, predominantly by affecting the Succinate (via Complex II)-linked electron transfer pathway. Lowering mt-tRF-LeuTAA impairs insulin secretion of rat and human pancreatic β-cells. Conclusions: Our findings indicate that mt-tRF-LeuTAA interacts with electron transfer system complexes and is a pivotal regulator of mitochondrial oxidative phosphorylation and its coupling to insulin secretion.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2212877824000863Test; https://doaj.org/toc/2212-8778Test

الوصول الحر: https://doaj.org/article/21f86b06ee584a01b80a33b6b969d246Test

المؤلفون: Cristina Cosentino, Romano Regazzi

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 4, p 1765 (2021)

مصطلحات موضوعية: pancreatic islet, macrophage, diabetes, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Macrophages are highly heterogeneous and plastic immune cells with peculiar characteristics dependent on their origin and microenvironment. Following pathogen infection or damage, circulating monocytes can be recruited in different tissues where they differentiate into macrophages. Stimuli present in the surrounding milieu induce the polarisation of macrophages towards a pro-inflammatory or anti-inflammatory profile, mediating inflammatory or homeostatic responses, respectively. However, macrophages can also derive from embryonic hematopoietic precursors and reside in specific tissues, actively participating in the development and the homeostasis in physiological conditions. Pancreatic islet resident macrophages are present from the prenatal stages onwards and show specific surface markers and functions. They localise in close proximity to β-cells, being exquisite sensors of their secretory ability and viability. Over the years, the crucial role of macrophages in β-cell differentiation and homeostasis has been highlighted. In addition, macrophages are emerging as central players in the initiation of autoimmune insulitis in type 1 diabetes and in the low-grade chronic inflammation characteristic of obesity and type 2 diabetes pathogenesis. The present work reviews the current knowledge in the field, with a particular focus on the mechanisms of communication between β-cells and macrophages that have been described so far.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/4/1765Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/0a2d6acecf7240ce809c8d224890faa5Test

المؤلفون: Carmela Iosco, Cristina Cosentino, Laura Sirna, Roberta Romano, Silvia Cursano, Alessandra Mongia, Giampaolo Pompeo, Julie di Bernardo, Claudio Ceccarelli, Giovanni Tallini, Kerry J. Rhoden

المصدر: Cellular Physiology and Biochemistry, Vol 34, Iss 3, Pp 966-980 (2014)

مصطلحات موضوعية: Thyroid gland, Iodide, Ion channel, Anoctamin, ANO1, TMEM16A, Physiology, QP1-981, Biochemistry, QD415-436

الوصف: Background/Aims: Iodide efflux from thyroid cells into the follicular lumen is essential for the synthesis of thyroid hormones, however, the pathways mediating this transport have only been partially identified. A calcium-activated pathway of iodide efflux has long been recognized, but its molecular identity unknown. Anoctamin 1 (ANO1) is a calcium-activated chloride channel (CaCC), and this study aims to investigate its contribution to iodide fluxes in thyroid cells. Methods: RT-PCR, immunohistochemistry, and live cell imaging with the fluorescent halide biosensor YFP-H148Q/I152L were used to study the expression, localization and function of ANO1 in thyroid cells. Results: ANO1 mRNA was detected in human thyroid tissue and FRTL-5 thyrocytes, and ANO1 protein was localized to the apical membrane of follicular cells. ATP induced a transient loss of iodide from FRTL-5 cells that was dependent on the mobilization of intracellular calcium, and was inhibited by CaCC/ANO1 inhibitors and siRNA against ANO1. Calcium-activated iodide efflux was also observed in CHO cells over-expressing the Sodium Iodide Symporter (NIS) and ANO1. Conclusion: ANO1 in thyrocytes functions as a calcium-activated channel mediating iodide efflux, and may contribute to the rapid delivery of iodide into the follicular lumen for the synthesis of thyroid hormones following activation by calcium-mobilizing stimuli.

وصف الملف: electronic resource

العلاقة: http://www.karger.com/Article/FullText/366313Test; https://doaj.org/toc/1015-8987Test; https://doaj.org/toc/1421-9778Test

الوصول الحر: https://doaj.org/article/f454c768902e4159b7167f2fd5e16e1dTest

المؤلفون: Benavente, Brenda Betania, Cosentino, Cristina Cosentino, Riego, Mariana

المصدر: Entramados : educación y sociedad; Vol. 7, Núm. 7 (2020); 83-91 ; 2422-6459

مصطلحات موضوعية: espacio público, construcción de ciudadanía, estado, gestión cultural

الوصف: El presente artículoi surge de un ensayo de investigación colectiva propuesta como ejercicio en la cátedra Metodologías y Prácticas de la Investigación en Cultura perteneciente a la Licenciatura en Gestión Cultural de la Universidad Nacional de Mar del Plata. La finalidad es la aproximación a la investigación cualitativa a partir de la construcción de un problema naciente de una coyuntura al cual podríamos aportar una mirada desde la Gestión Cultural. En Mar del Plata, como ha sucedido en otras ciudades, hace un tiempo se viene imponiendo una discusión sobre el uso y gestión de los espacios públicos, especialmente a partir del acercamiento de sectores privados con intereses sobre alguno de ellos. En este caso decidimos adentrarnos en las tensiones que genera un proyecto de cesión de uso de la Plaza del Agua1 a Espacio Clarín2 para la construcción de un “Polo Cultural”3. A través de la problemática indagamos algunas cuestiones que desconocíamos sobre el organigrama municipal y la jurisdicción de la plaza, como así también los imaginarios sociales que se construyen alrededor de la misma y la relevancia que presenta en relación a la construcción de ciudadanía. Como aprendizaje notamos que quedaron de lado algunas preguntas que nos hubiesen dirigido a la utilización de otras herramientas de investigación, por lo cual las conclusiones relevan sólo una parte del conflicto. Observamos además que la concepción del espacio público es una construcción inseparable del contexto y clima de época por lo cual existen ideas contrapuestas que según el marco político, económico y social siempre entran en tensión. i El presente artículo se concluyó en el mes de octubre del 2019. A principios del mes de noviembre vuelve el tema a circular en los portales de noticias con motivo de un proyecto que presentó en mesa de entrada del municipio solicitando su conseción. 1La Plaza del Agua es un espacio verde de la ciudad de Mar del Plata perteneciente a Obras Sanitarias (empresa municipal de servicios sanitarios). Está ubicado en la ...

وصف الملف: application/pdf

العلاقة: http://fh.mdp.edu.ar/revistas/index.php/entramados/article/view/3794/4456Test; http://fh.mdp.edu.ar/revistas/index.php/entramados/article/view/3794Test

الإتاحة: http://fh.mdp.edu.ar/revistas/index.php/entramados/article/view/3794Test

المؤلفون: Vyron Gorgogietas, Bahareh Rajaei, Chae Heeyoung, Bruno J. Santacreu, Sandra Marín-Cañas, Paraskevi Salpea, Toshiaki Sawatani, Anyishai Musuaya, María N. Arroyo, Cristina Moreno-Castro, Khadija Benabdallah, Celine Demarez, Sanna Toivonen, Cristina Cosentino, Nathalie Pachera, Maria Lytrivi, Ying Cai, Lode Carnel, Cris Brown, Fumihiko Urano, Piero Marchetti, Patrick Gilon, Decio L. Eizirik, Miriam Cnop, Mariana Igoillo-Esteve

المساهمون: UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition

المصدر: Diabetologia, Vol. 66, no.7, p. 1306-1321 (2023)

مصطلحات موضوعية: Mice, Knockout, Wolfram syndrome, GLP-1R agonists, Endocrinology, Diabetes and Metabolism, Induced Pluripotent Stem Cells, iPSC-derived neurons, Mice, Optic Atrophy, Insulin-Secreting Cells, Internal Medicine, Humans, Animals, Exenatide, Human pancreatic beta cells, iPSC-derived beta cells

الوصف: Aims/hypothesis Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons. Methods The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice. Results Our study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucose tolerance in WFS1-deficient mice, and that exenatide and dulaglutide improve beta cell function and prevent apoptosis in different human WFS1-deficient models including iPSC-derived beta cells from people with Wolfram syndrome. Exenatide improved mitochondrial function, reduced oxidative stress and prevented apoptosis in Wolfram syndrome iPSC-derived neural precursors and cerebellar neurons. Conclusions/interpretation Our study provides novel evidence for the beneficial effect of GLP-1R agonists on WFS1-deficient human pancreatic beta cells and neurons, suggesting that these drugs may be considered as a treatment for individuals with Wolfram syndrome. Graphical abstract

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c323abf826fb8049db46bad1f9fe4197Test
https://hdl.handle.net/2078.1/275993Test

المؤلفون: Mustafa Bilal, Bayazit, Cécile, Jacovetti, Cristina, Cosentino, Jonathan, Sobel, Kejing, Wu, Flora, Brozzi, Adriana, Rodriguez-Trejo, Lisa, Stoll, Claudiane, Guay, Romano, Regazzi

المصدر: Cell reports, vol. 40, no. 2, pp. 111069

مصطلحات موضوعية: RNA, Transfer, Insulin-Secreting Cells, Developmental biology, CP: Metabolism, diabetes, insulin, metabolism, pancreatic islet, transfer RNA [Animals, Cell Proliferation, Insulin Secretion, Insulin-Secreting Cells/metabolism, RNA/metabolism, RNA, Transfer/genetics, RNA, Transfer/metabolism, Rats, CP], Animals, RNA

الوصف: tRNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs with distinct cellular functions. Here, we studied the contribution of tRFs to the regulation of postnatal β cell maturation, a critical process that may lead to diabetes susceptibility in adulthood. We identified three tRFs abundant in neonatal rat islets originating from 5' halves (tiRNA-5s) of histidine and glutamate tRNAs. Their inhibition in these islets reduced β cell proliferation and insulin secretion. Mitochondrial respiration was also perturbed, fitting with the mitochondrial enrichment of nuclear-encoded tiRNA-5 HisGTG and tiRNA-5 GluCTC . Notably, tiRNA-5 inhibition reduced Mpc1, a mitochondrial pyruvate carrier whose knock down largely phenocopied tiRNA-5 inhibition. tiRNA-5 HisGTG interactome revealed binding to Musashi-1, which was essential for the mitochondrial enrichment of tiRNA-5 HisGTG . Finally, tiRNA-5s were dysregulated in the islets of diabetic and diabetes-prone animals. Altogether, tiRNA-5s represent a class of regulators of β cell maturation, and their deregulation in neonatal islets may lead to diabetes susceptibility in adulthood.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::e4336731b9e6e041c1712eee166e005cTest
https://serval.unil.ch/notice/serval:BIB_CD2CB954E2CDTest

المؤلفون: Miriam Cnop, Ioannis Gkantounas, Piero Marchetti, Ângela Castela, Sandra Marín-Cañas, Florian Szymczak, Mariana Igoillo-Esteve, Decio L. Eizirik, Maikel Luis Colli, Maria Inês Alvelos, Federica Fantuzzi, Lorella Marselli, Cristina Cosentino, Bianca Marmontel de Souza

المصدر: Islets
article-version (VoR) Version of Record

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism, Coefficient of variation, medicine.medical_treatment, Type 2 diabetes, Biology, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Endocrinology, Text mining, 0302 clinical medicine, Rt pcr analysis, Insulin-Secreting Cells, Pancreatic beta Cells, Reference genes, Gene expression, medicine, Humans, Beta (finance), Gene, 030304 developmental biology, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Genomics, medicine.disease, Molecular biology, Cytokine, RAB7A, 030220 oncology & carcinogenesis, Reference genes/ beta cells/ diabetes/ RNA-sequencing/ quantitative real-time pcr, Beta cell, business, 030217 neurology & neurosurgery, Research Article, Research Paper

الوصف: Exposure of human pancreatic beta cells to pro-inflammatory cytokines or metabolic stressors is used to model events related to type 1 and type 2 diabetes, respectively. Quantitative real-time PCR is commonly used to quantify changes in gene expression. The selection of the most adequate reference gene(s) for gene expression normalization is an important pre-requisite to obtain accurate and reliable results. There are no universally applicable reference genes, and the human beta cell expression of commonly used reference genes can be altered by different stressors. Here we aimed to identify the most stably expressed genes in human beta cells to normalize quantitative real-time PCR gene expression.We used comprehensive RNA-sequencing data from the human pancreatic beta cell line EndoC-βH1, human islets exposed to cytokines or the free fatty acid palmitate in order to identify the most stably expressed genes. Genes were filtered based on their level of significance (adjusted P-value >0.05), fold-change (|fold-change| We identified a total of 264 genes stably expressed in EndoC-βH1 cells and human islets following cytokine- or palmitate-induced stress, displaying a low coefficient of variation. Validation by quantitative real-time PCR of the top five genes ARF1, CWC15, RAB7A, SIAH1 and VAPA corroborated their expression stability under most of the tested conditions. Further validation in independent samples indicated that the geometric mean of ACTB and VAPA expression can be used as a reliable normalizing factor in human beta cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8be33f249fcf2de07402b0de5b98474fTest

المؤلفون: Romano Regazzi, Cristina Cosentino

المصدر: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 22, Iss 1765, p 1765 (2021)

مصطلحات موضوعية: 0301 basic medicine, 030209 endocrinology & metabolism, Inflammation, Review, macrophage, Biology, Catalysis, Inorganic Chemistry, Pathogenesis, lcsh:Chemistry, 03 medical and health sciences, 0302 clinical medicine, Immune system, Insulin-Secreting Cells, medicine, Macrophage, Animals, Homeostasis, Humans, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Cell Proliferation, geography, geography.geographical_feature_category, diabetes, Macrophages, Organic Chemistry, General Medicine, pancreatic islet, Islet, medicine.disease, Embryonic stem cell, Computer Science Applications, Cell biology, 030104 developmental biology, Diabetes Mellitus, Type 1, lcsh:Biology (General), lcsh:QD1-999, Diabetes Mellitus, Type 2, medicine.symptom, Insulitis

الوصف: Macrophages are highly heterogeneous and plastic immune cells with peculiar characteristics dependent on their origin and microenvironment. Following pathogen infection or damage, circulating monocytes can be recruited in different tissues where they differentiate into macrophages. Stimuli present in the surrounding milieu induce the polarisation of macrophages towards a pro-inflammatory or anti-inflammatory profile, mediating inflammatory or homeostatic responses, respectively. However, macrophages can also derive from embryonic hematopoietic precursors and reside in specific tissues, actively participating in the development and the homeostasis in physiological conditions. Pancreatic islet resident macrophages are present from the prenatal stages onwards and show specific surface markers and functions. They localise in close proximity to β-cells, being exquisite sensors of their secretory ability and viability. Over the years, the crucial role of macrophages in β-cell differentiation and homeostasis has been highlighted. In addition, macrophages are emerging as central players in the initiation of autoimmune insulitis in type 1 diabetes and in the low-grade chronic inflammation characteristic of obesity and type 2 diabetes pathogenesis. The present work reviews the current knowledge in the field, with a particular focus on the mechanisms of communication between β-cells and macrophages that have been described so far.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58d735f3bb079f8ae7d8af6aa38fe848Test
https://pubmed.ncbi.nlm.nih.gov/33578952Test

المؤلفون: Maria, Lytrivi, Elisa, De Franco, Hazem, Ibrahim, Hossam, Montaser, Matthew, Wakeling, Federica, Fantuzzi, Kashyap, Patel, Celine, Demarez, Ying, Cai, Mariana, Igoillo-Esteve, Cristina, Cosentino, Vaino, Lithovius, Helena, Vihinen, Eija, Jokitalo, Thomas, W Laver, Matthew, B Johnson, Toshiaki, Sawatani, Hadis, Shakeri, Nathalie, Pachera, Belma, Haliloglu, Mehmet, Nuri Ozbek, Edip, Unal, Ruken, Yildirim, Tushar, Godbole, Melek, Yildiz, Banu, Aydin, Angeline, Bilheu, Ikuo, Suzuki, Sarah, E Flanagan, Pierre, Vanderhaeghen, Valerie, Senee, Cecile, Julier, Piero, Marchetti, Decio, L Eizirik, Sian, Ellard, Jonna, Saarimaki-Vire, Timo, Otonkoski, Andrew, T Hattersley, Miriam, Cnop

المصدر: Endocrine Abstracts ; ISSN 1479-6848

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.1530/endoabs.71.003Test
http://www.endocrine-abstracts.org/ea/0071/ea0071003.htmTest

المؤلفون: Céline Derbois, Annabelle Chaussenot, Piero Marchetti, Cristina Cosentino, Laurence Ladrière, Toshiaki Sawatani, Baroj Abdulkarim, Cécile Julier, Pratibha Singh, Doris Lechner, Miriam Cnop, Anne Degavre, Sandra Marín-Cañas, Mariana Igoillo-Esteve, Maria Lytrivi, Valérie Senée, Anne Philippi, Paraskevi Salpea, Marc Nicolino, Jean-François Deleuze, Federica Fantuzzi, Lorella Marselli, Nathalie Pachera, Decio L. Eizirik

المصدر: European journal of endocrinology, 184 (3

مصطلحات موضوعية: Male, Microcephaly, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biologie générale, Apoptosis, Mice, 0302 clinical medicine, Endocrinology, Loss of Function Mutation, Insulin-Secreting Cells, Diabetes Mellitus, Type 1 -- genetics -- metabolism, Exome sequencing, Cells, Cultured, Apoptosis -- genetics, Neurodegeneration, Age Factors, General Medicine, Syndrome, Mitochondria, Pedigree, 030220 oncology & carcinogenesis, DNAJC3, Female, Biologie, Adult, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, 03 medical and health sciences, HSP40 Heat-Shock Proteins -- genetics, Diabetes mellitus, Internal medicine, medicine, Animals, Humans, Diabétologie, business.industry, Insulin, Endoplasmic reticulum, Biologie moléculaire, Enseignement des sciences, HSP40 Heat-Shock Proteins, medicine.disease, Rats, Diabetes Mellitus, Type 1, Mitochondria -- metabolism -- pathology, Biologie cellulaire, business, Insulin-Secreting Cells -- metabolism -- physiology

الوصف: DNAJC3, also known as P58IPK, is an Hsp40 family member that interacts with and inhibits PKR-like ER-localized eIF2α kinase (PERK). Dnajc3 deficiency in mice causes pancreatic β-cell loss and diabetes. Loss-of-function mutations in DNAJC3 cause early-onset diabetes and multisystemic neurodegeneration. The aim of our study was to investigate the genetic cause of early-onset syndromic diabetes in two unrelated patients, and elucidate the mechanisms of β-cell failure in this syndrome.
info:eu-repo/semantics/published

وصف الملف: 1 full-text file(s): application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16663b270bd28669ef83a4e231c827baTest
https://pubmed.ncbi.nlm.nih.gov/33486469Test