20.500.12556/DKUM-90992 Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices Many details of glucose-stimulated intracellular calcium changes in [beta] cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations. During activation, delays to activation of cells and any-cell-to-first-responder delays are shortened, and the sizes of simultaneously responding clusters increased with increasing glucose concentrations. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose concentration, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose concentration. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on [beta] cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling. NEW & NOTEWORTHY: We assessed concentration-dependence in coupled [beta] cells, degree of functional heterogeneity, and uncovered possible specialized subpopulations during the different phases of the response to glucose at the level of many individual cells. To this aim, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging over a wide range from threshold (7 mM) and physiological (8 and 9 mM) to supraphysiological (12 and 16 mM) glucose concentrations, classical physiological, and advanced network analyses. beta cells calcium imaging glucose-dependence network analysis beta celice kalcijevo slikanje glukozna odvisnost true false true American Physiological Society Angleški jezik Slovenski jezik Znanstveno delo 2024-10-15 11:23:48 2024-10-15 14:04:30 2024-10-16 03:14:01 0000-00-00 00:00:00 2021 0 0 Str. 305-323 št. 2 Letn. 321 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2021-02-04 2021-07-09 2021-08-09 612 75400451 10.1152/ajpendo.00043.2021 0193-1849 Stozer-2021-Glucose-dependent_activation,_acti.pdf Stozer-2021-Glucose-dependent_activation,_acti.pdf 1 1953BD452A93D2D0DEE8D5F986D2EAB8 093c67984770d6b13f1bc63a21a3399fb33066c869d15bff17eb34a940e143df 31fadb9a-8aed-11ef-9446-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=186512 https://doi.org/10.1152/ajpendo.00043.2021 0 31967d88-8ad7-11ef-9446-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=186508 Medicinska fakulteta Fakulteta za naravoslovje in matematiko 0 0 0