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Publication : Reduced synchroneity of intra-islet Ca<sup>2+</sup> oscillations in vivo in <i>Robo</i>-deficient β cells.

First Author  Adams MT Year  2021
Journal  Elife Volume  10
PubMed ID  34231467 Mgi Jnum  J:313724
Mgi Id  MGI:6727596 Doi  10.7554/eLife.61308
Citation  Adams MT, et al. (2021) Reduced synchroneity of intra-islet Ca(2+) oscillations in vivo in Robo-deficient beta cells. Elife 10:e61308
abstractText  The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among beta cells, yet testing this in vivo in the intact pancreas is challenging. Robo betaKO mice, in which the genes Robo1 and Robo2 are deleted selectively in beta cells, provide a unique model of altered islet spatial architecture without loss of beta cell differentiation or islet damage from diabetes. Combining Robo betaKO mice with intravital microscopy, we show here that Robo betaKO islets have reduced synchronized intra-islet Ca(2+) oscillations among beta cells in vivo. We provide evidence that this loss is not due to a beta cell-intrinsic function of Robo, mis-expression or mis-localization of Cx36 gap junctions, or changes in islet vascularization or innervation, suggesting that the islet architecture itself is required for synchronized Ca(2+) oscillations. These results have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.
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