Related Experiment Video
Updated: Jan 13, 2026
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Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
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TAS1R3 Regulates GTPase Signaling in Human Skeletal Muscle Cells for Glucose Uptake
Joseph M Hoolachan1, Rekha Balakrishnan1, Karla E Merz1
1Department of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute of City of Hope, Duarte, CA 91010, USA.
International Journal of Molecular Sciences
|January 10, 2026
Summary
Taste receptor type 1 member 3 (TAS1R3) is reduced in type 2 diabetes skeletal muscle. TAS1R3 regulates glucose uptake via Rac1, offering a potential therapeutic target for insulin sensitivity.
Area of Science:
- Endocrinology
- Metabolism
- Molecular Biology
Background:
- Taste receptor type 1 member 3 (TAS1R3), a G protein-coupled receptor (GPCR), is known for taste perception and insulin secretion.
- Its role in skeletal muscle glucose uptake, crucial for postprandial glucose disposal, is not well understood.
Purpose of the Study:
- To investigate the role of TAS1R3 in skeletal muscle glucose uptake.
- To explore the underlying signaling pathways and its potential as a therapeutic target in type 2 diabetes (T2D).
Main Methods:
- Assessed TAS1R3 expression in skeletal muscle from non-diabetic and T2D donors via qPCR and immunoblotting.
- Utilized pharmacological inhibition (lactisole) and siRNA knockdown of TAS1R3 in human myotubes.
- Measured insulin-stimulated glucose uptake and analyzed Rac1 activation, phospho-cofilin, and Gαq/11 signaling.
Main Results:
- TAS1R3 mRNA and protein levels were significantly lower in T2D skeletal muscle.
- Inhibition or knockdown of TAS1R3 impaired insulin-stimulated glucose uptake in myotubes.
- TAS1R3 regulates glucose uptake through a Rac1/phospho-cofilin pathway, independent of IRS1-AKT and Gαq/11 signaling.
Conclusions:
- TAS1R3 is downregulated in T2D skeletal muscle and plays a critical role in insulin-stimulated glucose uptake.
- TAS1R3 mediates glucose uptake via a novel non-canonical pathway involving Rac1.
- TAS1R3 represents a potential therapeutic target for enhancing insulin sensitivity in T2D.
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