Structural basis for delta cell paracrine regulation in pancreatic islets

Rafael Arrojo e Drigo; Stefan Jacob; Concha F. García-Prieto; Xiaofeng Zheng; Masahiro Fukuda; Hoa Tran Thi Nhu; Olga Stelmashenko; Flavia Letícia Martins Peçanha; Rayner Rodriguez-Diaz; Eric Bushong; Thomas Deerinck; Sebastien Phan; Yusuf Ali; Ingo Leibiger; Minni Chua; Thomas Boudier; Sang Ho Song; Martin Graf; George J. Augustine; Mark H. Ellisman; Per Olof Berggren

doi:10.1038/s41467-019-11517-x

Structural basis for delta cell paracrine regulation in pancreatic islets

Rafael Arrojo e Drigo, Stefan Jacob, Concha F. García-Prieto, Xiaofeng Zheng, Masahiro Fukuda, Hoa Tran Thi Nhu, Olga Stelmashenko, Flavia Letícia Martins Peçanha, Rayner Rodriguez-Diaz, Eric Bushong, Thomas Deerinck, Sebastien Phan, Yusuf Ali, Ingo Leibiger, Minni Chua, Thomas Boudier, Sang Ho Song, Martin Graf, George J. Augustine, Mark H. EllismanPer Olof Berggren

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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.

Original language	English (US)
Article number	3700
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11517-x
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Arrojo e Drigo, R., Jacob, S., García-Prieto, C. F., Zheng, X., Fukuda, M., Nhu, H. T. T., Stelmashenko, O., Peçanha, F. L. M., Rodriguez-Diaz, R., Bushong, E., Deerinck, T., Phan, S., Ali, Y., Leibiger, I., Chua, M., Boudier, T., Song, S. H., Graf, M., Augustine, G. J., ... Berggren, P. O. (2019). Structural basis for delta cell paracrine regulation in pancreatic islets. Nature communications, 10(1), [3700]. https://doi.org/10.1038/s41467-019-11517-x

Structural basis for delta cell paracrine regulation in pancreatic islets. / Arrojo e Drigo, Rafael; Jacob, Stefan; García-Prieto, Concha F.; Zheng, Xiaofeng; Fukuda, Masahiro; Nhu, Hoa Tran Thi; Stelmashenko, Olga; Peçanha, Flavia Letícia Martins; Rodriguez-Diaz, Rayner; Bushong, Eric; Deerinck, Thomas; Phan, Sebastien; Ali, Yusuf; Leibiger, Ingo; Chua, Minni; Boudier, Thomas; Song, Sang Ho; Graf, Martin; Augustine, George J.; Ellisman, Mark H.; Berggren, Per Olof.

In: Nature communications, Vol. 10, No. 1, 3700, 01.12.2019.

Research output: Contribution to journal › Article › peer-review

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 2019, 'Structural basis for delta cell paracrine regulation in pancreatic islets', Nature communications, vol. 10, no. 1, 3700. https://doi.org/10.1038/s41467-019-11517-x

Arrojo e Drigo, Rafael ; Jacob, Stefan ; García-Prieto, Concha F. ; Zheng, Xiaofeng ; Fukuda, Masahiro ; Nhu, Hoa Tran Thi ; Stelmashenko, Olga ; Peçanha, Flavia Letícia Martins ; Rodriguez-Diaz, Rayner ; Bushong, Eric ; Deerinck, Thomas ; Phan, Sebastien ; Ali, Yusuf ; Leibiger, Ingo ; Chua, Minni ; Boudier, Thomas ; Song, Sang Ho ; Graf, Martin ; Augustine, George J. ; Ellisman, Mark H. ; Berggren, Per Olof. / Structural basis for delta cell paracrine regulation in pancreatic islets. In: Nature communications. 2019 ; Vol. 10, No. 1.

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title = "Structural basis for delta cell paracrine regulation in pancreatic islets",

abstract = "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.",

author = "{Arrojo e Drigo}, Rafael and Stefan Jacob and Garc{\'i}a-Prieto, {Concha F.} and Xiaofeng Zheng and Masahiro Fukuda and Nhu, {Hoa Tran Thi} and Olga Stelmashenko and Pe{\c c}anha, {Flavia Let{\'i}cia Martins} and Rayner Rodriguez-Diaz and Eric Bushong and Thomas Deerinck and Sebastien Phan and Yusuf Ali and Ingo Leibiger and Minni Chua and Thomas Boudier and Song, {Sang Ho} and Martin Graf and Augustine, {George J.} and Ellisman, {Mark H.} and Berggren, {Per Olof}",

note = "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{\textquoteright}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 Let{\'i}cia Martins Pe{\c c}anha 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.",

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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

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.

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