Related Experiment Videos
PPAR-gamma gene expression is elevated in skeletal muscle of obese and type II diabetic subjects
K S Park1, T P Ciaraldi, L Abrams-Carter
1Department of Medicine, University of California at San Diego, La Jolla, USA.
Abstract:
The peroxisome proliferator activated receptor PPAR-gamma has been identified as a nuclear receptor for thiazolidenediones, which are compounds with insulin-sensitizing properties in several tissues, including skeletal muscle. To determine whether this receptor is expressed and possibly involved in insulin action/resistance in skeletal muscle, PPAR-gamma mRNA abundance and its regulation by insulin were quantified in muscle tissue and cultures from lean and obese nondiabetic and type II diabetic subjects using competitive reverse transcription-polymerase chain reaction (RT-PCR). In muscle biopsy specimens, PPAR-gamma mRNA was elevated in obese nondiabetic and type II diabetic subjects (23.4 +/- 4.2 and 28.0 +/- 5.69 x 10(3) copies/microg total RNA, respectively; both P < 0.05) compared with lean nondiabetic control subjects (9.4 +/- 2.3 x 10(3) copies/microg total RNA). Significant positive correlations were present among skeletal muscle PPAR-gamma mRNA levels, BMI (r = 0.67, P < 0.01), and fasting insulin concentration (r = 0.76, P < 0.001). PPAR-gamma mRNA levels were also elevated in muscle cultures from type II diabetic subjects compared with lean nondiabetic control subjects (330.1 +/- 52.9 vs. 192.1 +/- 27.0 x 10(3) copies/microg total RNA, P < 0.05). Insulin stimulation of muscle tissue (by hyperinsulinemic-euglycemic clamp for 3-4 h) or muscle cultures (30 nmol/l for 120 min) stimulated PPAR-gamma mRNA expression up to fourfold (10.0 +/- 2.7 to 41.3 +/- 7.4 x 10(3) copies/microg total RNA, P < 0.05, and 174.9 +/- 56.9 to 268.2 +/- 78.6 x 10(3) copies/microg total RNA, P < 0.05, respectively). In summary, PPAR-gamma mRNA expression in human skeletal muscle is acutely regulated by insulin and is increased in both obese nondiabetic and type II diabetic subjects in direct relation to BMI and fasting insulinemia. We conclude that abnormalities of PPAR-gamma may be involved in skeletal muscle insulin resistance of obesity and type II diabetes.
Insights
Peroxisome proliferator activated receptor (PPAR)-gamma mRNA is elevated in skeletal muscle of obese and type II diabetic individuals. Insulin acutely stimulates PPAR-gamma mRNA expression, suggesting its role in insulin resistance.
Area of Science:
- Molecular biology
- Endocrinology
- Metabolic research
Background:
- Peroxisome proliferator activated receptor (PPAR)-gamma is a nuclear receptor linked to insulin sensitization.
- Thiazolidinediones, insulin-sensitizing compounds, target PPAR-gamma.
- The role of PPAR-gamma in skeletal muscle insulin action and resistance is not fully understood.
Purpose of the Study:
- To investigate PPAR-gamma expression in human skeletal muscle.
- To determine the regulation of PPAR-gamma by insulin in skeletal muscle.
- To assess the potential involvement of PPAR-gamma in skeletal muscle insulin resistance associated with obesity and type II diabetes.
Main Methods:
- Quantification of PPAR-gamma mRNA abundance using competitive reverse transcription-polymerase chain reaction (RT-PCR).
- Analysis of muscle tissue and cultured muscle cells from lean, obese nondiabetic, and type II diabetic subjects.
- Insulin stimulation experiments using hyperinsulinemic-euglycemic clamp and direct insulin exposure in cultures.
Main Results:
- PPAR-gamma mRNA levels were significantly elevated in skeletal muscle of obese nondiabetic and type II diabetic subjects compared to lean controls.
- Skeletal muscle PPAR-gamma mRNA levels positively correlated with Body Mass Index (BMI) and fasting insulin concentration.
- Insulin acutely stimulated PPAR-gamma mRNA expression in both muscle tissue and cultured muscle cells.
Conclusions:
- PPAR-gamma mRNA expression in human skeletal muscle is acutely regulated by insulin.
- Increased PPAR-gamma mRNA is observed in obese and type II diabetic individuals, correlating with BMI and insulin levels.
- Aberrant PPAR-gamma expression may contribute to skeletal muscle insulin resistance in obesity and type II diabetes.