1. Dual mode of action of acetylcholine on cytosolic calcium oscillations in pancreatic beta and acinar cells in situNastja Sluga, Sandra Postić, Srdjan Sarikas, Ya-Chi Huang, Andraž Stožer, Marjan Rupnik, 2021, original scientific article Abstract: Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The supraphysiological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.
Keywords: pancreas tissue slices, acetylcholine, beta cell, acinar cell, Ca2+ oscillations
Published in DKUM: 14.10.2024; Views: 0; Downloads: 17
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2. Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levelsNastja Sluga, Lidija Križančić Bombek, Jasmina Kerčmar, Srdjan Sarikas, Sandra Postić, Johannes Pfabe, Maša Skelin, Dean Korošak, Andraž Stožer, Marjan Rupnik, 2022, original scientific article Abstract: 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.
Keywords: adrenaline, islets, beta cells, cAMP, concentration dependency, [Ca2+]c oscillations, forskolin
Published in DKUM: 04.07.2024; Views: 155; Downloads: 18
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