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Updated: Jul 16, 2026
Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Focal adhesion kinase regulates insulin resistance in skeletal muscle
1Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Chandigarh 160062, India.
Aims/Hypothesis:
On the basis of our previous studies, we investigated the possible role of focal adhesion kinase (FAK) in the development of insulin resistance in skeletal muscle, a major organ responsible for insulin-stimulated glucose uptake.
Materials And Methods:
Insulin-resistant C2C12 skeletal muscle cells were transfected with FAK wild-type or FAK mutant plasmids, knocked down using small interfering RNA (siRNA), and their effects on the levels and activities of insulin-signalling molecules and on glucose uptake were determined.
Results:
A significant decrease in tyrosine phosphorylation of FAK in insulin-resistant C2C12 cells was observed. A similar decrease was observed in skeletal muscle obtained from insulin-resistant Sprague-Dawley rats fed a high-fat diet. Increased levels of FAK in insulin-resistant C2C12 skeletal muscle cells increased insulin sensitivity and glucose uptake. These effects were reversed by an increase in the level of kinase activity mutant FAK or suppression of endogenous FAK by siRNA. FAK was also found to interact downstream with insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase C and glycogen synthase kinase 3beta, leading to translocation of glucose transporter 4 and resulting in the regulation of glucose uptake.
Conclusions/Interpretation:
The present study provides strong evidence that the modulation of FAK level regulates the insulin sensitivity of skeletal muscle cells. The results demonstrate a direct role of FAK in insulin-resistant skeletal muscle cells for the first time.
Insights
Focal adhesion kinase (FAK) plays a crucial role in regulating skeletal muscle insulin sensitivity. Modulating FAK levels can improve glucose uptake in insulin-resistant muscle cells, offering potential therapeutic targets.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Diseases
Background:
- Insulin resistance in skeletal muscle impairs glucose uptake, a key factor in type 2 diabetes.
- Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in various cellular processes.
Purpose of the Study:
- To investigate the role of FAK in the development of insulin resistance in skeletal muscle.
- To determine if FAK modulation affects insulin sensitivity and glucose uptake.
Main Methods:
- Insulin-resistant C2C12 skeletal muscle cells were manipulated using FAK wild-type/mutant plasmids and small interfering RNA (siRNA).
- Effects on insulin signaling molecules, FAK phosphorylation, and glucose uptake were assessed.
- Skeletal muscle from high-fat diet-fed rats was analyzed.
Main Results:
- Insulin-resistant cells and rat muscle showed decreased FAK tyrosine phosphorylation.
- Increasing FAK levels in resistant cells enhanced insulin sensitivity and glucose uptake.
- FAK interacts with key insulin signaling proteins, promoting glucose transporter 4 translocation.
Conclusions:
- FAK level modulation directly regulates skeletal muscle insulin sensitivity.
- This study establishes a novel role for FAK in insulin-resistant skeletal muscle cells.
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