In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, William C. Lemon, Jamien Shea, Soomin Kim, Richard T. Lee, Minoru Koyama, Philipp J. Keller, Loren L. Looger

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Article number109284
JournalCell Reports
Volume35
Issue number12
DOIs
StatePublished - Jun 22 2021

Keywords

  • Drosophila
  • astrocyte
  • biosensor
  • energy homeostasis
  • glucose
  • imaging
  • metabolism
  • neuron
  • transporters
  • zebrafish

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