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Structural and functional polarisation of human pancreatic beta cells in islets from organ donors with and without type 2 diabetes – published online 05/01/2021

Cottle GA

Louise Cottle, Wan Jun Gan, Ian Gilroy, Jaswinder S. Samra, Anthony J. Gill, Thomas Loudovaris, Helen E. Thomas, Wayne J. Hawthorne, Melkam A. Kebede, Peter Thorn

Accumulating evidence demonstrates that rodent beta cells are structurally and functional polarised. In this issue, Cottle et al ( investigated whether human beta cells are also polarised. This is an important question given the anatomical differences between rodent and human islets. The authors used pancreatic slices to preserve islet structure and 3D immunostaining to show that human beta cells are polarised with an apical–basal orientation, locating the basal pole of each cell at the capillary interface. Presynaptic scaffold proteins were enriched in this basal region, suggesting local specialisation for insulin granule exocytosis. The authors provide functional evidence indicating that the orientation of human beta cells is a focal adhesion-mediated response to extracellular matrix proteins secreted by capillary endothelial cells. They conclude that this evidence—that human beta cells are polarised—advances our understanding of normal islet function. They state that, clinically, these findings are relevant for understanding type 2 diabetes, in which islet capillary structure changes, and for cell-based treatments for type 1 diabetes.

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