Reduced synchroneity of intra-islet Ca2+ oscillations in vivo in Robo-deficient β cells.

The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among β cells, yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet spatial architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets have reduced synchronized intra-islet Ca2+ oscillations among β cells in vivo. We provide evidence that this loss is not due to a β 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 Ca2+ 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. © 2021, Adams et al.

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Melissa T Adams, JaeAnn M Dwulet, Jennifer K Briggs, Christopher A Reissaus, Erli Jin, Joseph M Szulczewski, Melissa R Lyman, Sophia M Sdao, Vira Kravets, Sutichot D Nimkulrat, Suzanne M Ponik, Matthew J Merrins, Raghavendra G Mirmira, Amelia K Linnemann, Richard Kp Benninger, Barak Blum. Reduced synchroneity of intra-islet Ca2+ oscillations in vivo in Robo-deficient β cells. eLife. 2021 Jul 07;10

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PMID: 34231467

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