20.500.12556/DKUM-89361 Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca2+ concentration ([Ca2+]c). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells. Here we report the effect of physiological adrenaline levels on [Ca2+]c dynamics in beta cell collectives in mice pancreatic tissue slice preparation. We used confocal microscopy with a high spatial and temporal resolution to evaluate glucose-stimulated [Ca2+]c events and their sensitivity to adrenaline. We investigated glucose concentrations from 8-20 mM to assess the concentration of adrenaline that completely abolishes [Ca2+]c events. We show that 8 mM glucose stimulation of beta cell collectives is readily inhibited by the concentration of adrenaline available under physiological conditions, and that sequent stimulation with 12 mM glucose or forskolin in high nM range overrides this inhibition. Accordingly, 12 mM glucose stimulation required at least an order of magnitude higher adrenaline concentration above the physiological level to inhibit the activity. To conclude, higher glucose concentrations stimulate beta cell activity in a non-linear manner and beyond levels that could be inhibited with physiologically available plasma adrenaline concentration. adrenaline islets beta cells cAMP concentration dependency [Ca2+]c oscillations forskolin adrenalin otočki beta celice odvisnost od koncentracije oscilacije [Ca2+]c forskolin true false true Frontiers Research Foundation Angleški jezik Slovenski jezik Znanstveno delo 2024-07-04 14:53:04 2024-07-04 15:07:26 2024-07-05 04:13:28 0000-00-00 00:00:00 2022 0 0 Str. 1-12 Letn. 13 Oct. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2022-08-07 2022-10-07 2022-10-25 612.349.7 131531011 10.3389/fendo.2022.1013697 1664-2392 Sluga-2022-Physiological_levels_of_adrenaline.pdf Sluga-2022-Physiological_levels_of_adrenaline.pdf 1 A2FA7CD92BE82E5B554A4CDB1AC08C15 e39a72083699db88e5e88e4febac01d996e20ae2209f8a9ec9e42b4f1dd76e5d 3b32320d-3a06-11ef-8f49-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=181144 https://doi.org/10.3389/fendo.2022.1013697 0 60ff1aa2-3a04-11ef-8f49-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=181143 Medicinska fakulteta 0 0 0