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

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Structural basis for delta cell paracrine regulation in pancreatic islets

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.10(1), pp.3700-12

2019-08-16

DOI: https://doi.org/10.1038/s41467-019-11517-x

PMCID: PMC6697679

PMID: 31420552

Abstract

Prediabetic State - metabolism

Optical Imaging

Pseudopodia - ultrastructure

Humans

Somatostatin-Secreting Cells - cytology

Optogenetics

Vascular Endothelial Growth Factor A - metabolism

Insulin-Secreting Cells - metabolism

Islets of Langerhans - metabolism

Islets of Langerhans - cytology

Insulin-Secreting Cells - cytology

Islets of Langerhans - ultrastructure

Prediabetic State - pathology

Somatostatin-Secreting Cells - ultrastructure

Intravital Microscopy

Islets of Langerhans - pathology

Paracrine Communication

Mice, Transgenic

Microscopy, Electron

Insulin-Secreting Cells - ultrastructure

Animals

Pseudopodia - metabolism

Mice

Blood Glucose - metabolism

Somatostatin-Secreting Cells - metabolism

Insulin-Like Growth Factor I - metabolism

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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.26 Diabetes; 1.26.361 Islets
Web Of Science research areas: Endocrinology & Metabolism
ESI research areas: Clinical Medicine

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Title: Structural basis for delta cell paracrine regulation in pancreatic islets
Creators: Rafael Arrojo E Drigo - Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, San Diego, 92037, USA
Stefan Jacob - Karolinska Intitutet, The Rolf Luft Research Center for Diabetes and Endocrinology, Stockholm, 171 77, Sweden
Concha F García-Prieto - Karolinska Intitutet, The Rolf Luft Research Center for Diabetes and Endocrinology, Stockholm, 171 77, Sweden
Xiaofeng Zheng - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Masahiro Fukuda - Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, 169857, Singapore
Hoa Tran Thi Nhu - Sorbonne University, UPMC University, Paris, 75005, France
Olga Stelmashenko - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Flavia Letícia Martins Peçanha - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, 21941-901, Brazil
Rayner Rodriguez-Diaz - Miller School of Medicine, University of Miami, Miami, 33136, USA
Eric Bushong - National Center for Microscopy and Imaging Research (NCMIR), University of California San Diego, San Diego, 92093, USA
Thomas Deerinck - National Center for Microscopy and Imaging Research (NCMIR), University of California San Diego, San Diego, 92093, USA
Sebastien Phan - National Center for Microscopy and Imaging Research (NCMIR), University of California San Diego, San Diego, 92093, USA
Yusuf Ali - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Ingo Leibiger - Karolinska Intitutet, The Rolf Luft Research Center for Diabetes and Endocrinology, Stockholm, 171 77, Sweden
Minni Chua - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Thomas Boudier - Sorbonne University, UPMC University, Paris, 75005, France
Sang-Ho Song - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Martin Graf - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
George J Augustine - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore
Mark H Ellisman - National Center for Microscopy and Imaging Research (NCMIR), University of California San Diego, San Diego, 92093, USA
Per-Olof Berggren - Miller School of Medicine, University of Miami, Miami, 33136, USA. per-olof.berggren@ki.se
Publication Details: Nature communications, Vol.10(1), pp.3700-12
Publisher: England
Academic Unit: Miller School of Medicine; Diabetes Research Institute (DRI); UMMG Department of Surgery; UMMG Dept of Medicine - Endocrinology, Diabetes & Metabolism
Language: English
Resource Type: Journal article
PMID: 31420552
PMCID: PMC6697679
Record Identifier: 991031577286402976