Journal
CELL REPORTS
Volume 35, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109284
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- Howard Hughes Medical Institute
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A family of highly sensitive glucose sensors was described to study glucose transport and metabolism in cells. Differential glucose kinetics were observed in different cell types, revealing the existence of specific transport pathways for intracellular glucose flux.
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 mu M 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 similar to 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.
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