학술논문
Reduced synchroneity of intra-islet Ca.sup.2+ oscillations in vivo in Robo-deficient [beta] cells
Document Type
Academic Journal
Author
Adams, Melissa T; Dwulet, JaeAnn M; Briggs, Jennifer K; Reissaus, Christopher A; Jin, Erli; Szulczewski, Joseph M; Lyman, Melissa R; Sdao, Sophia M; Kravets, Vira; Nimkulrat, Sutichot D; Ponik, Suzanne M; Merrins, Matthew J; Mirmira, Raghavendra G; Linnemann, Amelia K; Benninger, Richard KP; Blum, Barak
Source
eLife. July 7, 2021, Vol. 10
Subject
Language
English
ISSN
2050-084X
Abstract
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 [beta]KO 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 [beta]KO mice with intravital microscopy, we show here that Robo [beta]KO islets have reduced synchronized intra-islet Ca.sup.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.sup.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.
Byline: 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 [...]
Byline: 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 [...]