TY - JOUR
T1 - Structural basis for delta cell paracrine regulation in pancreatic islets
AU - Arrojo e Drigo, Rafael
AU - Jacob, Stefan
AU - García-Prieto, Concha F.
AU - Zheng, Xiaofeng
AU - Fukuda, Masahiro
AU - Nhu, Hoa Tran Thi
AU - Stelmashenko, Olga
AU - Peçanha, Flavia Letícia Martins
AU - Rodriguez-Diaz, Rayner
AU - Bushong, Eric
AU - Deerinck, Thomas
AU - Phan, Sebastien
AU - Ali, Yusuf
AU - Leibiger, Ingo
AU - Chua, Minni
AU - Boudier, Thomas
AU - Song, Sang Ho
AU - Graf, Martin
AU - Augustine, George J.
AU - Ellisman, Mark H.
AU - Berggren, Per-Olof Ynge
N1 - Funding Information:
This work was supported by the Lee Kong Chian School of Medicine, Nanyang Technological University start-up grant to Per-Olof Berggren, the Lee Foundation grant, the Swedish Research Council, the Family Erling-Persson Foundation, the Novo Nordisk Foundation, the Stichting af Jochnick Foundation, the Swedish Diabetes Association, the Scandia Insurance Company Ltd., Diabetes Research and Wellness Foundation, Berth von Kantzow’s Foundation, the Strategic Research Program in Diabetes at Karolinska Institutet, the ERC-2013-AdG 338936-Betalmage, and the Knut and Alice Wallenberg Foundation. Rafael Arrojo e Drigo was supported by a research fellowship from the Nanyang Structural Biology Institute (NISB) and by an AXA Research Fund postdoctoral fellowship. Flavia Letícia Martins Peçanha was supported by a grant from the National Council for Scientific and Technological Development—Brazil (CNPq). The authors would like to thank Javier Chow from The Salk Institute for assistance with implementing MATLAB scrips for delta cell activity analysis. P-OB is co-founder and CEO of Biocrine, an unlisted biotech company that is using the ACE technique as a research tool, S.J. was employed by Biocrine AB and I.L. is a consultant for Biocrine AB. Open access funding provided by Karolinska Institute.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 Ca2+ 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.
AB - 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 Ca2+ 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.
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U2 - 10.1038/s41467-019-11517-x
DO - 10.1038/s41467-019-11517-x
M3 - Article
C2 - 31420552
AN - SCOPUS:85070794625
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3700
ER -