Related Experiment Video
Updated: Nov 6, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
Tmod3 Phosphorylation Mediates AMPK-Dependent GLUT4 Plasma Membrane Insertion in Myoblasts
Man Mohan Shrestha1, Chun-Yan Lim1, Xuezhi Bi2
1Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Tropomodulin 3 (Tmod3) is identified as a novel AMPK effector that mediates glucose uptake in muscle cells. Tmod3 regulates glucose transporter 4 (GLUT4) translocation and insertion into the plasma membrane, crucial for muscle glucose homeostasis.
Area of Science:
- Muscle physiology
- Cellular metabolism
- Molecular biology
Background:
- Insulin and muscle contractions stimulate glucose uptake in skeletal muscles by promoting glucose transporter 4 (GLUT4) translocation to the plasma membrane.
- AMP-activated protein kinase (AMPK) activation during muscle contraction enhances GLUT4 translocation, but its direct effectors remain largely unknown.
Purpose of the Study:
- To identify novel AMPK effectors involved in regulating GLUT4 translocation.
- To elucidate the role of these effectors in AMPK-dependent glucose uptake in muscle cells.
Main Methods:
- Biochemical assays
- Molecular biology techniques
- Fluorescent microscopy imaging
- Gain- and loss-of-function mutants of tropomodulin 3 (Tmod3) were utilized.
Main Results:
- Tropomodulin 3 (Tmod3) was identified as a novel AMPK substrate.
- Tmod3 acts as a crucial mediator of AMPK-dependent GLUT4 translocation and glucose uptake in myoblasts.
- Tmod3 is essential for AMPK-induced F-actin remodeling and GLUT4 insertion into the plasma membrane.
Conclusions:
- Tmod3 is a key AMPK effector regulating GLUT4 insertion into the plasma membrane and glucose uptake in muscle cells.
- This study provides new mechanistic insights into glucose homeostasis regulation in muscle.
- Tmod3 represents a potential therapeutic target for metabolic disorders.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
cAMP-dependent Protein Kinase Pathways
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
MAPK Signaling Cascades
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Microtubule Associated Proteins (MAPs)

