Table 2.
Effects of PPAR agonists on metabolic parameters in obese and lean ZDF rats
| Pre-clamp | Post-clamp | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Treatment | Insulin (μU ml−1) | Glucose (mM) | HOMA-IR | HOMA-β (%) | Pancreatic insulin (nmol g−1) | Pancreatic insulin/plasma glucose | FFA (mM) | TG (mM) | Leptin (ng ml−1) |
| Prevention study in ZDF | |||||||||
| CON | 16.2±1.8 | 22.8±1.5 | 16.4±2.3 | 17.8±2.9 | 2.8±0.8 | 0.10±0.03 | 1.23±0.10 | 3.97±0.77 | 6.5±0.6 |
| BF | 15.0±4.4 | 23.0±1.6 | 16.2±5.0 | 15.0±4.2 | 3.9±0.9 | 0.13±0.04 | 0.96±0.12 | 1.63±0.47** | 6.6±0.6 |
| PIO | 13.3±0.9 | 7.4±0.7*** | 4.5±0.6** | 71.6±12.2 | 5.8±2.1 | 0.60±0.21** | 0.57±0.04*** | 0.91±0.10*** | 12.2±1.1*** |
| RAGA | 15.9±2.7 | 7.2±0.6*** | 4.7±0.7** | 125.9±40.2** | 5.2±0.9 | 0.56±0.15** | 0.60±0.06*** | 1.11±0.09*** | 12.5±1.2*** |
| LEAN | 7.3±0.9** | 6.3±0.5** | 1.9±0.2* | 56.1±12.1** | 4.5±0.8 | 0.77±0.17** | 0.70±0.09** | 0.80±0.13** | 2.7±0.3*** |
| Intervention study in ZDF | |||||||||
| CON | 15.3±2.3 | 23.9±1.6 | 16.6±3.3 | 13.0±1.3 | 1.2±0.3 | 0.06±0.02 | 1.17±0.10 | 3.38±0.45 | 5.8±0.2 |
| BF | 14.8±1.9 | 19.9±1.8 | 13.3±2.6 | 19.8±3.3 | 1.1±0.5 | 0.04±0.01 | 1.01±0.10 | 2.90±0.69 | 5.2±0.2 |
| PIO | 18.3±2.9 | 11.0±1.2*** | 9.2±2.2 | 55.9±10.2** | 2.2±0.4 | 0.21±0.05* | 0.61±0.07*** | 1.15±0.15** | 8.0±0.4* |
| RAGA | 15.4±1.4 | 10.4±1.5*** | 6.8±0.8* | 60.4±12.9** | 2.9±1.0 | 0.21±0.06 | 0.62±0.03*** | 1.59±0.23* | 9.7±1.1** |
| LEAN | 15.2±0.4 | 6.7±0.5** | 4.6±0.4** | 105.6±15.7** | 2.4±0.4 | 0.36±0.08** | 0.51±0.10** | 0.92±0.19** | 3.1±0.4*** |
| Intervention study in DIO | |||||||||
| CON | 9.8±1.5 | 6.3±0.3 | 2.8±0.5 | 74.7±12.5 | 5.8±2.4 | 0.55±0.12 | 1.97±0.10 | 1.90±0.15 | 6.8±0.7 |
| BF | 6.4±2.0 | 7.8±1.1 | 2.5±1.2 | 36.9±7.6 | 7.3±2.2 | 0.93±0.30 | 1.21±0.12*** | 1.09±0.14*** | 5.2±1.0 |
| PIO | 6.8±1.1 | 4.7±0.9 | 1.3±0.3 | 37.8±4.7 | 5.9±1.2 | 1.69±0.55 | 0.70±0.04*** | 0.78±0.04*** | 7.4±0.6 |
| RAGA | 8.4±1.2 | 5.4±1.1 | 2.0±0.4 | 104.5±39.6 | 4.6±1.0 | 0.79±0.26 | 0.90±0.07*** | 0.93±0.09*** | 7.2±0.6 |
| CHOW | 5.1±0.3** | 6.4±0.5 | 1.4±0.1* | 43.6±9.7 | 1.8±0.4* | 0.28±0.09 | 1.22±0.04** | 1.00±0.011** | 3.2±0.4** |
Animals were treated for 28 days with ragaglitazar (RAGA, 1.5 mg kg−1), pioglitazone (PIO, 30 mg kg−1) and bezafibrate (BF, 100 mg kg−1). Values are expressed as mean±s.e.m. (n=8);
*
P<0.05;
**
P<0.01;
***
P⩽0.0001 as compared to obese control (CON). HOMA-IR=insulin resistance index=glucose (mM) × insulin (μU ml−1)/22.5; HOMA-β=insulin secretion index=20 × insulin (μU ml−1)/(glucose (mM)-3.5). Pancreatic insulin/plasma glucose ratio=(nmol g−1)/mM (fasting plasma glucose).