Dynamic Uni- and Multicellular Patterns Encode Biphasic Activity in Pancreatic Islets
Autor: | Julien Gaitan, Domenico Bosco, Eléonore Bertin, Fanny Lebreton, Daniel Cattaert, Bogdan Catargi, Sylvie Renaud, Matthieu Raoux, Emilie Puginier, Sandra Oucherif, Jochen Lang, Antoine Pirog, Manon Jaffredo |
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Přispěvatelé: | Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Glucagon-Like Peptide 1 / metabolism Type 2 / metabolism Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism [SDV.BC]Life Sciences [q-bio]/Cellular Biology Inbred C57BL 03 medical and health sciences Islets of Langerhans Mice Insulin / metabolism 0302 clinical medicine Insulin Secretion / genetics Insulin Secretion / physiology Glucagon-Like Peptide 1 Insulin-Secreting Cells Insulin Secretion Diabetes Mellitus Internal Medicine medicine Glucose homeostasis Animals Humans Insulin Secretion ComputingMilieux_MISCELLANEOUS Islets of Langerhans / metabolism geography geography.geographical_feature_category ddc:617 Chemistry Pancreatic islets Vesicle [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology [CHIM.MATE]Chemical Sciences/Material chemistry Islet Postprandial Period Insulin-Secreting Cells / metabolism Cell biology Coupling (electronics) Electrophysiology Mice Inbred C57BL Multicellular organism 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 2 |
Zdroj: | Diabetes Diabetes, American Diabetes Association, 2021, 70 (4), pp.878-888. ⟨10.2337/db20-0214⟩ Diabetes, Vol. 70, No 4 (2021) pp. 878-888 |
ISSN: | 0012-1797 |
DOI: | 10.2337/db20-0214⟩ |
Popis: | Biphasic secretion is an autonomous feature of many endocrine micro-organs to fulfill physiological demands. The biphasic activity of islet β-cells maintains glucose homeostasis and is altered in type 2 diabetes. Nevertheless, underlying cellular or multicellular functional organizations are only partially understood. High-resolution noninvasive multielectrode array recordings permit simultaneous analysis of recruitment, of single-cell, and of coupling activity within entire islets in long-time experiments. Using this unbiased approach, we addressed the organizational modes of both first and second phase in mouse and human islets under physiological and pathophysiological conditions. Our data provide a new uni- and multicellular model of islet β-cell activation: during the first phase, small but highly active β-cell clusters are dominant, whereas during the second phase, electrical coupling generates large functional clusters via multicellular slow potentials to favor an economic sustained activity. Postprandial levels of glucagon-like peptide 1 favor coupling only in the second phase, whereas aging and glucotoxicity alter coupled activity in both phases. In summary, biphasic activity is encoded upstream of vesicle pools at the micro-organ level by multicellular electrical signals and their dynamic synchronization between β-cells. The profound alteration of the electrical organization of islets in pathophysiological conditions may contribute to functional deficits in type 2 diabetes. |
Databáze: | OpenAIRE |
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