iGlucoSnFR2: A genetically encoded fluorescent sensor for measuring intracellular or extracellular glucose in vivo in mouse brain

TL;DR

A new fluorescent sensor called iGlucoSnFR2 can measure glucose levels inside and outside cells in the mouse brain, offering high-resolution insights into glucose dynamics.

Contribution

iGlucoSnFR2 is a second-generation sensor that improves on the original by enabling in vivo measurements of both intracellular and extracellular glucose in live mice.

Findings

iGlucoSnFR2 reports intracellular glucose consumption and gluconeogenesis in cell culture.

The sensor outperforms the original iGlucoSnFR in detecting glucose changes in the mouse brain in vivo.

Membrane-targeted iGlucoSnFR2 can measure absolute extracellular glucose concentration in awake mice.

Abstract

Continuous glucose monitors have proven invaluable for monitoring blood glucose levels for diabetics, but they are of limited use for observing glucose dynamics at the cellular (or subcellular) level. We have developed a second generation, genetically encoded intensity-based glucose sensing fluorescent reporter (iGlucoSnFR2). We show that when it is targeted to the cytosol, it reports intracellular glucose consumption and gluconeogenesis in cell culture, along with efflux from the endoplasmic reticulum. It outperforms the original iGlucoSnFR in vivo when observed by fiber photometry in mouse brain and reports transient increase in glucose concentration when stimulated by noradrenaline or electrical stimulation. Last, we demonstrate that membrane localized iGlucoSnFR2 can be calibrated in vivo to indicate absolute changes in extracellular glucose concentration in awake mice. We anticipate iGlucoSnFR2 facilitating previously unobservable measurements of glucose dynamics with high spatial and temporal resolution in living mammals and other experimental organisms.

Genetically encoded fluorescent sensor reports extracellular or intracellular glucose fluctuations in mouse brains in vivo.

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