High-speed calcium imaging in the zebrafish pancreas reveals how beta- cells regulate glucose levels in vivo

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Abstract Summary

Pancreatic beta-cells are the main regulators of glucose levels in higher organisms. However, our understanding of beta-cell function comes with two caveats. First, monitoring beta-cell function with single-cell resolution in their native environment, in which beta-cells are innervated and vascularized and in constant communication with the metabolic state of the organism, remains very challenging. Second, it is difficult to mimic in an ex vivo setting the progressive increase in glucose levels that takes place after a meal in vivo. Thus, how beta-cell respond to endogenous blood sugar remains a mystery due to the difficulties to visualize beta-cell activity in vivo. We have developed a high-resolution, high speed protocol for calcium imaging of beta-cells in vivo using transgenic zebrafish expressing GCAMP6s under the insulin promoter. Remarkably, we find that endogenously, beta-cells exhibit rapid oscillations in calcium. Several experimental manipulations support the role of these oscillations in regulating glucose levels. First, they are rapidly inhibited in response to glucose lowering via insulin injection. Secondly, beta-cell activity ceases rapidly in response to temporal silencing of the circulation due to optogenetic and mechanical block of the heartbeat. Moreover, blocking the calcium oscillations leads to hyperglycemia. To test whether beta-cells are equal in their glucose-responsiveness in vivo, we developed a setup for temporally controlled increases in glucose levels. Using high-speed imaging, our results document the presence of leader and follower beta-cell subpopulations. Currently, we are applying optogenetics and selective cell ablations to define whether the leader cells control the activity of the rest of the beta-cells in the islet. Thus, our approach shines light on the true response of beta-cells to increases in glucose concentrations in vivo.

Submission ID :
IDS61297
Submission Type
Abstract Topics
Technische Universität Dresden

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Professor Jay Skyler
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Dr Sarah Richardson
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Dr Richard Oram
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Dr Helena Elding Larsson
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KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

Contact
British Society for Immunology
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