Structural basis for delta cell paracrine regulation in pancreatic islets

被引：90

作者：

Arrojo e Drigo, Rafael ^{[1
,10
]}

Jacob, Stefan ^{[2
]}

Garcia-Prieto, Concha F. ^{[2
]}

Zheng, Xiaofeng ^{[1
]}

Fukuda, Masahiro ^{[3
]}

Hoa Tran Thi Nhu ^{[4
,5
,6
]}

Stelmashenko, Olga ^{[1
]}

Martins Pecanha, Flavia Leticia ^{[7
]}

Rodriguez-Diaz, Rayner ^{[8
]}

Bushong, Eric ^{[9
]}

Deerinck, Thomas ^{[9
]}

Phan, Sebastien ^{[9
]}

Ali, Yusuf ^{[1
]}

Leibiger, Ingo ^{[2
]}

Chua, Minni ^{[1
]}

Boudier, Thomas ^{[4
,5
,6
]}

Song, Sang-Ho ^{[1
]}

Graf, Martin ^{[1
]}

Augustine, George J. ^{[1
]}

Ellisman, Mark H. ^{[9
]}

Berggren, Per-Olof ^{[1
,2
,7
]}

机构：

[1] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 636921, Singapore

[2] Karolinska Intitutet, Rolf Luft Res Ctr Diabet & Endocrinol, S-17177 Stockholm, Sweden

[3] Duke NUS Med Sch, Signature Program Neurosci & Behav Disorders, Mol Neurophysiol Lab, Singapore 169857, Singapore

[4] Bioinformat Inst ASTAR, Singapore 138632, Singapore

[5] IPAL, Singapore 138632, Singapore

[6] UPMC Univ, Sorbonne Univ, F-75005 Paris, France

[7] Univ Fed Rio de Janeiro, BR-21941901 Rio de Janeiro, Brazil

[8] Univ Miami, Miller Sch Med, Miami, FL 33136 USA

[9] Univ Calif San Diego, NCMIR, San Diego, CA 92093 USA

[10] Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

瑞典研究理事会;

关键词：

GLUCOSE-INDUCED SOMATOSTATIN; POSITIVE AUTOCRINE SIGNAL; GLUCAGON-SECRETION; INSULIN-SECRETION; ALPHA-CELLS; BETA-CELLS; LANGERHANS; MOUSE; ARCHITECTURE; INNERVATION;

D O I：

10.1038/s41467-019-11517-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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