We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far.
COBISS.SI-ID: 512264760
In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose.
COBISS.SI-ID: 512254008
Authors describe that specific activation of PKA changes the sensitivity of the exocytotic machinery to calcium. The paper originally describes the role of hormones. e.g. GLP-1, which increase intracellular cAMP levels, thus significantly enhancing insulin release at a give glucose concentration.
COBISS.SI-ID: 66514689
Authors describe that even though Munc18-1 emerges as the key SM-protein determining the Ca2+ threshold for triggering secretory activity in a stimulated beta-cell, Munc18-2 has the ability to increase Ca2+ sensitivity and thus mediates the release of fusion-competent granules requiring a lower cytoplasmic-free Ca2+ concentration. Hence, Munc18-1 and Munc18-2 display distinct subcellular compartmentalization and can coordinate the insulin exocytotic process differently as a consequence of the actual [Ca2+]i.
COBISS.SI-ID: 512148536
Authors describe a novel mechanism through which serotonin influences insulin release from pancreatic beta cells. Some key proteins in the process of exocytosis of insulin become covalently bound to serotonin and prematurely enter the protein degradation pathway.
COBISS.SI-ID: 63941377