Insulin sensitization by small molecules enhancing GLUT4 translocation

Terry C Yin; Jonathan G Van Vranken; Dhiraj Srivastava; Ayushi Mittal; Paul Buscaglia; Autumn E Moore; Jissele A Verdinez; Aschleigh E Graham; Susan A Walsh; Michael A Acevedo; Robert J Kerns; Nikolai O Artemyev; Steven P Gygi; Julien A Sebag

doi:10.1016/j.chembiol.2023.06.012

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Insulin sensitization by small molecules enhancing GLUT4 translocation

Journal article

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Insulin sensitization by small molecules enhancing GLUT4 translocation

Terry C Yin, Jonathan G Van Vranken, Dhiraj Srivastava, Ayushi Mittal, Paul Buscaglia, Autumn E Moore, Jissele A Verdinez, Aschleigh E Graham, Susan A Walsh, Michael A Acevedo, …

Cell chemical biology, Vol.30(8), pp.933-942.e6

08/2023

DOI: 10.1016/j.chembiol.2023.06.012

PMCID: PMC11191318

PMID: 37453421

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11191318/pdf/nihms-1998977.pdfView

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Abstract

Insulin resistance (IR) is the root cause of type II diabetes, yet no safe treatment is available to address it. Using a high throughput compatible assay that measures real-time translocation of the glucose transporter glucose transporter 4 (GLUT4), we identified small molecules that potentiate insulin action. In vivo, these insulin sensitizers improve insulin-stimulated GLUT4 translocation, glucose tolerance, and glucose uptake in a model of IR. Using proteomic and CRISPR-based approaches, we identified the targets of those compounds as Unc119 proteins and solved the structure of Unc119 bound to the insulin sensitizer. This study identifies compounds that have the potential to be developed into diabetes treatment and establishes Unc119 proteins as targets for improving insulin sensitivity.

Details

Title: Subtitle: Insulin sensitization by small molecules enhancing GLUT4 translocation
Creators: Terry C Yin - University of Iowa
Jonathan G Van Vranken - Harvard University
Dhiraj Srivastava - University of Iowa
Ayushi Mittal - University of Iowa
Paul Buscaglia - University of Iowa
Autumn E Moore - University of Iowa
Jissele A Verdinez - University of Iowa
Aschleigh E Graham - University of Iowa
Susan A Walsh - University of Iowa
Michael A Acevedo - University of Iowa
Robert J Kerns - University of Iowa
Nikolai O Artemyev - University of Iowa
Steven P Gygi - Harvard University
Julien A Sebag - University of Iowa
Resource Type: Journal article
Publication Details: Cell chemical biology, Vol.30(8), pp.933-942.e6
DOI: 10.1016/j.chembiol.2023.06.012
PMID: 37453421
PMCID: PMC11191318
NLM abbreviation: Cell Chem Biol
ISSN: 2451-9456
eISSN: 2451-9448
Language: English
Electronic publication date: 07/2023
Date published: 08/2023
Academic Unit: Radiology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Medicinal and Natural Products Chemistry; Ophthalmology and Visual Sciences
Record Identifier: 9984445014102771

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