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Dynamic Uni- and Multicellular Patterns Encode Biphasic Activity in Pancreatic Islets
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Edité par CCSD ; American Diabetes Association -
International audience. Biphasic secretion is an autonomous feature of many endocrine micro-organs to fulfill physiological demands. The biphasic activity of islet b-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 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 b-cell activation: during the first phase, small but highly active b-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 microorgan level by multicellular electrical signals and their dynamic synchronization between b-cells. The profound alteration of the electrical organization of islets in pathophysiological conditions may contribute to functional deficits in type 2 diabetes.
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