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

Jonathan S Marvin; Philipp Mächler; Chengbo Meng; Tayfun Ates; Ronak H Patel; Raghabendra Adhikari; Monika A Makurath; Zaneta Ku; Daniel Feliciano; Deniz Atasoy; Guohong Cui; David Kleinfeld; Timothy A Brown

doi:10.1126/sciadv.adz3889

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

Journal article

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

Jonathan S Marvin, Philipp Mächler, Chengbo Meng, Tayfun Ates, Ronak H Patel, Raghabendra Adhikari, Monika A Makurath, Zaneta Ku, Daniel Feliciano, Deniz Atasoy, …

Science advances, Vol.11(46), eadz3889

11/14/2025

DOI: 10.1126/sciadv.adz3889

PMCID: PMC12609159

PMID: 41223288

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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.

Animals

Biosensing Techniques - methods

Brain - metabolism

Endoplasmic Reticulum - metabolism

Genes, Reporter

Glucose - metabolism

Humans

Mice

Details

Title: Subtitle: iGlucoSnFR2: A genetically encoded fluorescent sensor for measuring intracellular or extracellular glucose in vivo in mouse brain
Creators: Jonathan S Marvin - Janelia Research Campus
Philipp Mächler - University of California San Diego
Chengbo Meng - National Institute of Environmental Health Sciences
Tayfun Ates - University of Iowa
Ronak H Patel - Janelia Research Campus
Raghabendra Adhikari - Janelia Research Campus
Monika A Makurath - Janelia Research Campus
Zaneta Ku - University of California San Diego
Daniel Feliciano - Janelia Research Campus
Deniz Atasoy - University of Iowa
Guohong Cui - National Institute of Environmental Health Sciences
David Kleinfeld - University of California San Diego
Timothy A Brown - Janelia Research Campus
Resource Type: Journal article
Publication Details: Science advances, Vol.11(46), eadz3889
DOI: 10.1126/sciadv.adz3889
PMID: 41223288
PMCID: PMC12609159
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: AAAS
Grant note: National Institute of Neurological Disorders and Stroke: U19 NS123717 Intramural Research Program of the NIH/NIEHS of the United States: ZIA-ES103310 Swiss National Science Foundation: P500PB_211149 NIH: R01DK126740
This work is supported by the Swiss National Science Foundation P500PB_211149 (to P.M.), U19 NS123717/NS/NINDS NIH HHS/United States (to P.M.),tje NIH grant R01DK126740 (to D.A.), and the Intramural Research Program of the NIH/NIEHS of the United States grant ZIA-ES103310 (to G.C.).
Language: English
Date published: 11/14/2025
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9985027460102771

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