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Optogenetic control of insulin secretion by pancreatic β-cells in vitro and in vivo

Gene Therapy volume 22, pages 553–559 (2015)Cite this article

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Abstract

The present study assessed the ability of optogenetics techniques to provide a better understanding of the control of insulin secretion, particularly regarding pancreatic β-cell function in homeostasis and pathological conditions such as diabetes mellitus (DM). We used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations ([Ca2+]i) in a mouse pancreatic β-cell line (MIN6) transfected with the optogenetic protein channelrhodopsin-2 (ChR2). The ChR2-transfected MIN6 (ChR2-MIN6) cells secreted insulin following irradiation with a laser (470 nm). The increase in [Ca2+]i was accompanied by elevated levels of messenger RNAs that encode calcium/calmodulin-dependent protein kinase II delta and adenylate cyclase 1. ChR2-MIN6 cells suspended in matrigel were inoculated into streptozotocin-induced diabetic mice that were then subjected to a glucose tolerance test. Laser irradiation of these mice caused a significant decrease in blood glucose, and the irradiated implanted cells expressed insulin. These findings demonstrate the power of optogenetics to precisely and efficiently controlled insulin secretion by pancreatic β-cells ‘on demand', in contrast to techniques using growth factors or chemical inducers. Optogenetic technology shows great promise for understanding the mechanisms of glucose homeostasis and for developing treatments for metabolic diseases such as DM.

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Acknowledgements

This work was supported by The Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid Project for Scientific Research on Innovative Areas 'Crosstalk between transcriptional control and energy pathways, mediated by hub metabolites' (26116728) and Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Young Scientists (A) (25713009).

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  1. Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan

    T Kushibiki, S Okawa, T Hirasawa & M Ishihara

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  1. T Kushibiki
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Correspondence to T Kushibiki.

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Kushibiki, T., Okawa, S., Hirasawa, T. et al. Optogenetic control of insulin secretion by pancreatic β-cells in vitro and in vivo. Gene Ther 22, 553–559 (2015). https://doi.org/10.1038/gt.2015.23

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