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

Area of Science:

• Metabolic Imaging
• Molecular Biology
• Neuroscience

Background:

• Glucose is central to metabolism, and its dysregulation is implicated in diseases like diabetes.
• Existing methods for measuring glucose often lack the spatial and temporal resolution needed for dynamic biological processes.

Purpose of the Study:

• To develop and characterize a novel family of single-wavelength genetically encoded glucose sensors.
• To utilize these sensors for high-resolution imaging of glucose dynamics in various biological systems.

Main Methods:

• Development of genetically encoded sensors with tunable affinities (1 μM to 10 mM) and fast kinetics.
• Application of sensors in cultured cells, neuron/glia co-cultures, Drosophila larval CNS, and zebrafish models.
• High-resolution imaging to track glucose influx, efflux, and metabolism.

Main Results:

• Sensors demonstrated high signal-to-noise ratio and fast kinetics.
• Observed approximately 3-fold faster glucose changes in astrocytes compared to neurons.
• Identified a rostro-caudal glucose transport pathway in Drosophila CNS.
• Visualized glucose dynamics in response to physiological stimuli (insulin, epinephrine) and perturbations in zebrafish.

Conclusions:

• The developed glucose sensors provide unprecedented capabilities for studying glucose metabolism with high spatial and temporal resolution.
• These tools are valuable for mechanistic characterization of glucose transporters and metabolic pathways in diverse biological contexts.
• The sensors will facilitate in vivo imaging of glucose dynamics in behaving animals, offering new insights into metabolic regulation.