DHEA administration and exercise training improves insulin resistance in obese rats

Background: Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats. Methods: After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group). Results: After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 +/- 6.5 mg/dL; DHEA, 102 +/- 9.5 mg/dL; control, 148 +/- 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 +/- 0.11; exercise, 0.337 +/- 0.16%; DHEA, 0.331 +/- 0.14; control, 0.308 +/- 0.12). Muscular DHEA and 5 alpha-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01). Conclusion: These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations.