Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo

Research output: Contribution to journalArticle

Standard

Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo. / Salem, Victoria; Delgadillo Silva, Luis; Suba, Kinga; Georgiades, Eleni; Mousavy Gharavy, S. Neda; Akhtar, Nadeem; Martin-Alonso, Aldara; Gaboriau, David C. A.; Rothery, Stephen M.; Stylianides, Theodoros; Carrat, Gaelle; Pullen, Timothy J.; Pal Singh, Sumeet; Hodson, David; Leclerc, Isabelle; Shapiro, A. M. James; Marchetti, Piero; Briant, Linford J. B.; Distaso, Walter; Ninov, Nikolay; Rutter, Guy A.

In: Nature, Vol. 1, 14.06.2019, p. 615-629.

Research output: Contribution to journalArticle

Harvard

Salem, V, Delgadillo Silva, L, Suba, K, Georgiades, E, Mousavy Gharavy, SN, Akhtar, N, Martin-Alonso, A, Gaboriau, DCA, Rothery, SM, Stylianides, T, Carrat, G, Pullen, TJ, Pal Singh, S, Hodson, D, Leclerc, I, Shapiro, AMJ, Marchetti, P, Briant, LJB, Distaso, W, Ninov, N & Rutter, GA 2019, 'Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo', Nature, vol. 1, pp. 615-629. https://doi.org/10.1038/s42255-019-0075-2

APA

Salem, V., Delgadillo Silva, L., Suba, K., Georgiades, E., Mousavy Gharavy, S. N., Akhtar, N., Martin-Alonso, A., Gaboriau, D. C. A., Rothery, S. M., Stylianides, T., Carrat, G., Pullen, T. J., Pal Singh, S., Hodson, D., Leclerc, I., Shapiro, A. M. J., Marchetti, P., Briant, L. J. B., Distaso, W., ... Rutter, G. A. (2019). Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo. Nature, 1, 615-629. https://doi.org/10.1038/s42255-019-0075-2

Vancouver

Salem V, Delgadillo Silva L, Suba K, Georgiades E, Mousavy Gharavy SN, Akhtar N et al. Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo. Nature. 2019 Jun 14;1:615-629. https://doi.org/10.1038/s42255-019-0075-2

Author

Salem, Victoria ; Delgadillo Silva, Luis ; Suba, Kinga ; Georgiades, Eleni ; Mousavy Gharavy, S. Neda ; Akhtar, Nadeem ; Martin-Alonso, Aldara ; Gaboriau, David C. A. ; Rothery, Stephen M. ; Stylianides, Theodoros ; Carrat, Gaelle ; Pullen, Timothy J. ; Pal Singh, Sumeet ; Hodson, David ; Leclerc, Isabelle ; Shapiro, A. M. James ; Marchetti, Piero ; Briant, Linford J. B. ; Distaso, Walter ; Ninov, Nikolay ; Rutter, Guy A. / Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo. In: Nature. 2019 ; Vol. 1. pp. 615-629.

Bibtex

@article{e8c67afb7b054e588edf1d8383e04d47,
title = "Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo",
abstract = "Pancreatic β-cells form highly connected networks within isolated islets. Whether this behaviour pertains to the situation in vivo, after innervation and during continuous perfusion with blood, is unclear. In the present study, we used the recombinant Ca2+ sensor GCaMP6 to assess glucose-regulated connectivity in living zebrafish Danio rerio, and in murine or human islets transplanted into the anterior eye chamber. In each setting, Ca2+ waves emanated from temporally defined leader β-cells, and three-dimensional connectivity across the islet increased with glucose stimulation. Photoablation of zebrafish leader cells disrupted pan-islet signalling, identifying these as likely pacemakers. Correspondingly, in engrafted mouse islets, connectivity was sustained during prolonged glucose exposure, and super-connected {\textquoteleft}hub{\textquoteright} cells were identified. Granger causality analysis revealed a controlling role for temporally defined leaders, and transcriptomic analyses revealed a discrete hub cell fingerprint. We thus define a population of regulatory β-cells within coordinated islet networks in vivo. This population may drive Ca2+ dynamics and pulsatile insulin secretion.",
keywords = "pancreatic islet, zebrafish, functional imaging, ca2+ dynamics, GCaMP6, β cell, in vivo, connectivity, photo-ablation, transcriptomics, cluster analysis, Granger causality",
author = "Victoria Salem and {Delgadillo Silva}, Luis and Kinga Suba and Eleni Georgiades and {Mousavy Gharavy}, {S. Neda} and Nadeem Akhtar and Aldara Martin-Alonso and Gaboriau, {David C. A.} and Rothery, {Stephen M.} and Theodoros Stylianides and Gaelle Carrat and Pullen, {Timothy J.} and {Pal Singh}, Sumeet and David Hodson and Isabelle Leclerc and Shapiro, {A. M. James} and Piero Marchetti and Briant, {Linford J. B.} and Walter Distaso and Nikolay Ninov and Rutter, {Guy A.}",
year = "2019",
month = jun
day = "14",
doi = "10.1038/s42255-019-0075-2",
language = "English",
volume = "1",
pages = "615--629",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo

AU - Salem, Victoria

AU - Delgadillo Silva, Luis

AU - Suba, Kinga

AU - Georgiades, Eleni

AU - Mousavy Gharavy, S. Neda

AU - Akhtar, Nadeem

AU - Martin-Alonso, Aldara

AU - Gaboriau, David C. A.

AU - Rothery, Stephen M.

AU - Stylianides, Theodoros

AU - Carrat, Gaelle

AU - Pullen, Timothy J.

AU - Pal Singh, Sumeet

AU - Hodson, David

AU - Leclerc, Isabelle

AU - Shapiro, A. M. James

AU - Marchetti, Piero

AU - Briant, Linford J. B.

AU - Distaso, Walter

AU - Ninov, Nikolay

AU - Rutter, Guy A.

PY - 2019/6/14

Y1 - 2019/6/14

N2 - Pancreatic β-cells form highly connected networks within isolated islets. Whether this behaviour pertains to the situation in vivo, after innervation and during continuous perfusion with blood, is unclear. In the present study, we used the recombinant Ca2+ sensor GCaMP6 to assess glucose-regulated connectivity in living zebrafish Danio rerio, and in murine or human islets transplanted into the anterior eye chamber. In each setting, Ca2+ waves emanated from temporally defined leader β-cells, and three-dimensional connectivity across the islet increased with glucose stimulation. Photoablation of zebrafish leader cells disrupted pan-islet signalling, identifying these as likely pacemakers. Correspondingly, in engrafted mouse islets, connectivity was sustained during prolonged glucose exposure, and super-connected ‘hub’ cells were identified. Granger causality analysis revealed a controlling role for temporally defined leaders, and transcriptomic analyses revealed a discrete hub cell fingerprint. We thus define a population of regulatory β-cells within coordinated islet networks in vivo. This population may drive Ca2+ dynamics and pulsatile insulin secretion.

AB - Pancreatic β-cells form highly connected networks within isolated islets. Whether this behaviour pertains to the situation in vivo, after innervation and during continuous perfusion with blood, is unclear. In the present study, we used the recombinant Ca2+ sensor GCaMP6 to assess glucose-regulated connectivity in living zebrafish Danio rerio, and in murine or human islets transplanted into the anterior eye chamber. In each setting, Ca2+ waves emanated from temporally defined leader β-cells, and three-dimensional connectivity across the islet increased with glucose stimulation. Photoablation of zebrafish leader cells disrupted pan-islet signalling, identifying these as likely pacemakers. Correspondingly, in engrafted mouse islets, connectivity was sustained during prolonged glucose exposure, and super-connected ‘hub’ cells were identified. Granger causality analysis revealed a controlling role for temporally defined leaders, and transcriptomic analyses revealed a discrete hub cell fingerprint. We thus define a population of regulatory β-cells within coordinated islet networks in vivo. This population may drive Ca2+ dynamics and pulsatile insulin secretion.

KW - pancreatic islet

KW - zebrafish

KW - functional imaging

KW - ca2+ dynamics

KW - GCaMP6

KW - β cell

KW - in vivo

KW - connectivity

KW - photo-ablation

KW - transcriptomics

KW - cluster analysis

KW - Granger causality

U2 - 10.1038/s42255-019-0075-2

DO - 10.1038/s42255-019-0075-2

M3 - Article

VL - 1

SP - 615

EP - 629

JO - Nature

JF - Nature

SN - 0028-0836

ER -