20.500.12556/DKUM-88814 The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. Cyclic adenosine monophosphate (cAMP) amplifies stimulus-secretion coupling via protein kinase A and guanine nucleotide exchange protein 2 (Epac2A). With the present research, we aimed to clarify the influence of cAMP-elevating diterpene forskolin on cytoplasmic calcium dynamics and intercellular network activity, which are two of the crucial elements of normal beta cell stimulus-secretion coupling, and the role of Epac2A under normal and stimulated conditions. To this end, we performed functional multicellular calcium imaging of beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Forskolin evoked calcium signals in otherwise substimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and stimulation with forskolin increased the active time via an increase in oscillation frequency and a decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of stimulation with forskolin in preventing a decline in beta cell functional connectivity with time. Finally, stimulation with forskolin prolonged beta cell activity during deactivation, especially in Epac2A knock-out mice. pancreas tissue slices beta cells calcium imaging amplifying pathway forskolin Epac2A KO intercellular network trebušna slinavka tkivne rezine beta celice slikanje kalcija ojačevalna pot forskolin medcelično omrežje true false true Frontiers Research Foundation Angleški jezik Slovenski jezik Znanstveno delo 2024-05-27 12:14:35 2024-05-27 12:33:22 2024-05-28 03:30:27 0000-00-00 00:00:00 2023 0 0 Str. 1-14 Št. članka 1225486 Letn. 14 Avg. 2023 0000-00-00 Zaloznikova Objavljeno apc 2023-05-19 2023-08-08 2023-08-28 612.349.7 163143427 10.3389/fendo.2023.1225486 1664-2392 Klemen-2023-The_effect_of_forskolin_and_the_ro.pdf Klemen-2023-The_effect_of_forskolin_and_the_ro.pdf 1 5FA1E7D4A63AC94990D869610F1D7311 a775c46bd32f4d4cc0b3d8634f4962c534fe0b60793c18ded6c025621aa19e65 31bf6fb7-1c14-11ef-a1ea-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=179790 https://doi.org/10.3389/fendo.2023.1225486 0 f2438adb-1c11-11ef-a1ea-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=179789 Medicinska fakulteta Fakulteta za naravoslovje in matematiko 0 0 0