In vivo monitoring of intracellular Ca2+ dynamics in the pancreatic β-cells of zebrafish embryos.

Abstract:

:Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca2+ sensor in pancreatic β-cells to monitor a key step in glucose induced insulin secretion; the elevations of intracellular [Ca2+]i. In vivo and ex vivo analyses of [Ca2+]i demonstrate that β-cell responsiveness to glucose is well established in late embryogenesis and that embryonic β-cells also respond to free fatty acid and amino acid challenges. In vivo imaging of whole embryos further shows that indirect glucose administration, for example by yolk injection, results in a slow and asynchronous induction of β-cell [Ca2+]i responses, while intravenous glucose injections cause immediate and islet-wide synchronized [Ca2+]i fluctuations. Finally, we demonstrate that embryos with disrupted mutation of the CaV1.2 channel gene cacna1c are hyperglycemic and that this phenotype is associated with glucose-independent [Ca2+]i fluctuation in β-cells. The data reveal a novel central role of cacna1c in β-cell specific stimulus-secretion coupling in zebrafish and demonstrate that the novel approach we propose - to monitor the [Ca2+]i dynamics in embryonic β-cells in vivo - will help to expand the understanding of β-cell physiological functions in healthy and diseased states.

journal_name

Islets

journal_title

Islets

authors

Lorincz R,Emfinger CH,Walcher A,Giolai M,Krautgasser C,Remedi MS,Nichols CG,Meyer D

doi

10.1080/19382014.2018.1540234

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

221-238

issue

6

eissn

1938-2014

issn

1938-2022

journal_volume

10

pub_type

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