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PPAR-gamma expression modulates insulin sensitivity in C2C12 skeletal muscle cells
Navin K Verma1, Jaskirat Singh, Chinmoy S Dey
1Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160 062, India.
British Journal of Pharmacology
|October 27, 2004
Summary
Muscle Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a direct role in insulin sensitivity. Overexpressing PPAR-gamma in skeletal muscle cells enhances glucose uptake and may treat insulin resistance.
Area of Science:
- Metabolic disease research
- Molecular biology of skeletal muscle
Background:
- Skeletal muscle is a key tissue for glucose homeostasis and insulin sensitivity.
- Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression is low in skeletal muscle, and its role in insulin sensitivity is unclear.
- Previous studies showed insulin resistance in mice with muscle-specific PPAR-gamma deletion, but whole-animal effects were possible.
Purpose of the Study:
- To investigate the direct role of muscle PPAR-gamma in insulin sensitivity.
- To determine if modulating PPAR-gamma expression affects glucose uptake in skeletal muscle cells.
- To assess the impact of PPAR-gamma on insulin-resistant muscle cells.
Main Methods:
- Stable transfection of C2C12 skeletal muscle cells with PPAR-gamma sense or antisense constructs.
- Assessment of glucose uptake using 2-deoxyglucose incorporation.
- Examination of cells under normal and insulin-resistant conditions with varying PPAR-gamma expression.
Main Results:
- Inhibition of PPAR-gamma induced insulin resistance in C2C12 cells.
- Overexpression of PPAR-gamma significantly increased glucose uptake in response to insulin and pioglitazone.
- PPAR-gamma overexpressing insulin-resistant cells showed substantially enhanced glucose uptake compared to wild-type cells.
Conclusions:
- PPAR-gamma is directly involved in insulin sensitization within skeletal muscle cells.
- Modulating PPAR-gamma expression impacts glucose uptake and insulin sensitivity.
- Pharmacological overexpression of muscle PPAR-gamma may be a therapeutic strategy for insulin resistance.