The effects of (+)-Z-bisdehydrodoisynolic acid on diabetic phenotype in female obese Zucker rats.

摘要

The putative selective estrogen receptor modulator (+)-Z-bisdehydrodoisynolic acid ((+)-Z-BDDA) has been found to lower cardiovascular risk factors in rodents; however, its antidiabetic effects were not previously defined. The purpose of this study was to investigate the anti-diabetic effectiveness of (+)-Z-BDDA in an insulin resistant rodent model. Female obese Zucker rats were randomly assigned to two dietary groups for 10 weeks: control (C) or 1.8 mg of (+)-Z-BDDA/kg diet (CB). At week 9, animals were subjected to an oral glucose tolerance test (OGTT) followed by indirect calorimetry. At sacrifice, physiological, biochemical, and molecular parameters were examined. CB animals gained less weight, had reduced food intake and exhibited an altered metabolic rate (P<0.05) as compared to C rats. The CB rats also had a lower RQ as compared to the controls, suggesting greater fatty acid oxidation. Moreover, the OGTT revealed a marked improvement in glucose tolerance (15, 30 and 60 min) in CB-treated animals when compared to C animals. Compared to the CB group, C rats exhibited higher plasma cholesterol. We are currently examining gene-expression profiles. Overall, these results suggest that (+)-Z-BDDA may have clinical applications in treating insulin-resistance, type 2 diabetes mellitus, and obesity.