Islet architecture controls synchronous β cell response to glucose in the intact mouse pancreas in vivo
Adams, M. T.; Reissaus, C. A.; Szulczewski, J. M.; Dwulet, J. M.; Lyman, M. R.; Sdao, S. M.; Nimkulrat, S. D.; Ponik, S. M.; Merrins, M. J.; Benninger, R. K. P.; Mirmira, R. G.; Linnemann, A. K.; Blum, B.
Show abstract
The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion between {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 lose synchronized intra-islet Ca2+ oscillations between {beta} cells in vivo. We provide evidence that this loss is not due to a {beta} cell-intrinsic function of Robo, loss of Connexin36 gap junctions, or changes in islet vascularization, 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.
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