@article{be0311011ab54488bd844f544bf3b2c3,
title = "In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor",
abstract = "Glucose is arguably the most important molecule in metabolism, and its dysregulation underlies diabetes. We describe a family of single-wavelength genetically encoded glucose sensors with a high signal-to-noise ratio, fast kinetics, and affinities varying over four orders of magnitude (1 μM to 10 mM). The sensors allow mechanistic characterization of glucose transporters expressed in cultured cells with high spatial and temporal resolution. Imaging of neuron/glia co-cultures revealed ∼3-fold faster glucose changes in astrocytes. In larval Drosophila central nervous system explants, intracellular neuronal glucose fluxes suggested a rostro-caudal transport pathway in the ventral nerve cord neuropil. In zebrafish, expected glucose-related physiological sequelae of insulin and epinephrine treatments were directly visualized. Additionally, spontaneous muscle twitches induced glucose uptake in muscle, and sensory and pharmacological perturbations produced large changes in the brain. These sensors will enable rapid, high-resolution imaging of glucose influx, efflux, and metabolism in behaving animals.",
keywords = "Drosophila, astrocyte, biosensor, energy homeostasis, glucose, imaging, metabolism, neuron, transporters, zebrafish",
author = "Keller, {Jacob P.} and Marvin, {Jonathan S.} and Haluk Lacin and Lemon, {William C.} and Jamien Shea and Soomin Kim and Lee, {Richard T.} and Minoru Koyama and Keller, {Philipp J.} and Looger, {Loren L.}",
note = "Funding Information: We would like to thank Jay Unruh for ImageJ plugins; Gary Yellen, Jim Truman, Tim Ryan, and Phil Borden for helpful discussions; Deepika Walpita and Kathy Schaefer for cell culture; the Janelia Fly Facility for fly maintenance; and Jared Rouchard & the Janelia Aquarium Facility for zebrafish maintenance. We thank Dr. Michael Pack (University of Pennsylvania) for the kind gift of p5E-fabp10a. We thank Gaby Paez for help making the graphical abstract. This work was funded by the Howard Hughes Medical Institute. J.P.K. J.S.M. S.K. R.T.L. and L.L.L. conceived, designed, and constructed the sensor and variations thereof. J.P.K. J.S.M. and S.K. characterized the sensor in purified protein. J.P.K. J.S.M. H.L. W.C.L. J.S. M.K. P.J.K. and L.L.L. contributed to the design of cellular and animal experiments. J.P.K. J.S. H.L. and W.C.L. generated experimental animals, prepared, and/or conducted physiological experiments. J.P.K. J.S.M. W.C.L. M.K. and L.L.L. analyzed the data. J.P.K. J.S.M. and L.L.L. wrote the manuscript, with input from the other authors. L.L.L. J.S.M. and R.T.L. are holders of US Patent US9939437B2, which covers iGlucoSnFR. The remaining authors declare no competing interests. Funding Information: We would like to thank Jay Unruh for ImageJ plugins; Gary Yellen, Jim Truman, Tim Ryan, and Phil Borden for helpful discussions; Deepika Walpita and Kathy Schaefer for cell culture; the Janelia Fly Facility for fly maintenance; and Jared Rouchard & the Janelia Aquarium Facility for zebrafish maintenance. We thank Dr. Michael Pack (University of Pennsylvania) for the kind gift of p5E-fabp10a. We thank Gaby Paez for help making the graphical abstract. This work was funded by the Howard Hughes Medical Institute . Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jun,
day = "22",
doi = "10.1016/j.celrep.2021.109284",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
number = "12",
}