Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon
| العنوان: | Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon |
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| المؤلفون: | K. Burda-Jacob, C. Berlé, S. Ducreux, Anne-Marie Madec, C. Thivolet, C. Crola Da Silva, Jennifer Rieusset, L. Païta, F. Van Coppenolle, Muhammad Rizwan Alam, Florian Dingreville, K. Chikh, R. Al-Mawla, Marie-Agnès Chauvin, R. Cassel |
| المساهمون: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), INSERM . Universite Claude Bernard Lyon1, JDRF award (ECIT Islet for Basic Research program) from the Geneva University Hospital [31-2008-413], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL) |
| المصدر: | PLoS ONE PLoS ONE, Public Library of Science, 2016, 11 (2), pp.e0148686. ⟨10.1371/journal.pone.0148686⟩ Plos One 2 (11), 1-17. (2016) PLoS ONE, Vol 11, Iss 2, p e0148686 (2016) |
| بيانات النشر: | HAL CCSD, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, [SDV]Life Sciences [q-bio], Palmitates, lcsh:Medicine, Apoptosis, Endoplasmic Reticulum, Biochemistry, Calcium in biology, Ion Channels, Mice, 0302 clinical medicine, Endocrinology, Genes, Reporter, Insulin-Secreting Cells, Insulin Secretion, Medicine and Health Sciences, Homeostasis, Insulin, RNA, Small Interfering, lcsh:Science, Endoplasmic Reticulum Chaperone BiP, Cells, Cultured, Heat-Shock Proteins, Calcium signaling, Multidisciplinary, Secretory Pathway, Cell Death, Physics, Endoplasmic Reticulum Stress, 3. Good health, Type 2 Diabetes, Electrophysiology, Protein Transport, medicine.anatomical_structure, Lipotoxicity, Cell Processes, Caspases, Physical Sciences, Protein Translocation Systems, Puromycin, RNA Interference, Cellular Structures and Organelles, Anisomycin, Research Article, canal pancréatique, medicine.medical_specialty, diabète de type 2, Endocrine Disorders, Bone and Mineral Metabolism, Recombinant Fusion Proteins, Biophysics, chemistry.chemical_element, Neurophysiology, 030209 endocrinology & metabolism, Biology, Calcium, Transfection, 03 medical and health sciences, Internal medicine, medicine, Diabetes Mellitus, Animals, Humans, Calcium Signaling, RNA, Messenger, réticulum endoplasmique, insuline, Calcium metabolism, Diabetic Endocrinology, Ion Transport, Endocrine Physiology, Endoplasmic reticulum, Pancreatic islets, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, Hormones, Enzyme Activation, 030104 developmental biology, Metabolism, chemistry, Metabolic Disorders, Unfolded protein response, lcsh:Q, Calcium Channels, Physiological Processes, Neuroscience |
| الوصف: | International audience; Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8922a8fb7c6fee86431f1e291529d6cdTest https://hal.archives-ouvertes.fr/hal-01850368/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8922a8fb7c6fee86431f1e291529d6cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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