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.