Structural basis for delta cell paracrine regulation in pancreatic islets.

Arrojo E Drigo R, Jacob S, García-Prieto CF, Zheng X, Fukuda M, Nhu HTT, Stelmashenko O, Peçanha FLM, Rodriguez-Diaz R, Bushong E, Deerinck T, Phan S, Ali Y, Leibiger I, Chua M, Boudier T, Song SH, Graf M, Augustine GJ, Ellisman MH, Berggren PO
Nat Commun. 2019 10 (1): 3700

PMID: 31420552 · PMCID: PMC6697679 · DOI:10.1038/s41467-019-11517-x

Little is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions.

MeSH Terms (17)

Animals Blood Glucose Humans Insulin-Like Growth Factor I Insulin-Secreting Cells Intravital Microscopy Islets of Langerhans Mice Mice, Transgenic Microscopy, Electron Optical Imaging Optogenetics Paracrine Communication Prediabetic State Pseudopodia Somatostatin-Secreting Cells Vascular Endothelial Growth Factor A

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