Synchronized β cell response to glucose is lost concomitant with loss of islet architecture in Robo deficient islets of Langerhans in vivo

The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion between β cells, yet testing this in the intact pancreas is challenging. mice, in which the genes and 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 mice with intravital microscopy, we show here that islets lose synchronized intra-islet Ca oscillations between β cells . We provide evidence that this loss is not due to a β 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 Ca 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.