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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Small-Molecule Tyrosine Kinase Inhibitors Modulate Glucose Handling in C2C12 Cell Line In Vitro: A Mechanistic Study.
Takudzwa Mugiya1, Samarah Zvandasara1, Mmamosheledi Mothibe1
1Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa.
Pharmaceuticals (Basel, Switzerland)
|October 29, 2025
Summary
Small-molecule tyrosine kinase inhibitors (SMTKIs) impact glucose metabolism in C2C12 cells by affecting glucose uptake, AKT expression, and GLUT4 translocation. Dasatinib shows potential for antidiabetic applications, warranting further investigation into SMTKI effects on metabolic homeostasis.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Small-molecule tyrosine kinase inhibitors (SMTKIs) are used in cancer chemotherapy.
- SMTKIs have variable effects on glycaemic control, with some causing hypoglycemia and others hyperglycemia.
- This study investigates the in vitro effects of SMTKIs on glucose metabolism in C2C12 cells.
Purpose of the Study:
- To elucidate how SMTKIs affect glucose metabolism in C2C12 cells.
- To investigate the impact of SMTKIs on glucose uptake, AKT expression, GLUT4 expression and translocation, and IL-6 expression.
- To assess the effects of SMTKIs on insulin-stimulated AKT phosphorylation and GLUT4 translocation.
Main Methods:
- C2C12 skeletal muscle cells were treated with imatinib, dasatinib, axitinib, and erlotinib for 24 hours.
- Cell viability was assessed using MTT assay.
- Glucose uptake, AKT and GLUT4 expression, and IL-6 expression were measured using ELISA and glucometer readings.
Main Results:
- SMTKIs did not affect C2C12 cell viability.
- Imatinib showed a concentration-dependent increase in glucose uptake, while axitinib, dasatinib, and erlotinib had no significant effect compared to control.
- SMTKIs increased GLUT4 translocation and AKT expression, but did not alter GLUT4 expression. IL-6 expression was elevated.
Conclusions:
- SMTKIs, particularly dasatinib, influence glucose metabolism in C2C12 cells through effects on GLUT4 translocation and AKT expression.
- Dasatinib exhibits potential antidiabetic properties.
- Further research is necessary to understand the broader implications of SMTKI on metabolic homeostasis and potential therapeutic strategies.
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