Hyperandrogenism Rat Model Construction And Exploration Of The Glucose Metabolism Phenotype

Diabetes is a metabolic disease characterized by high blood glucose levels and caused by absolute or relative insulin deficiency.At present,diabetes has become a major global healthcare problem.Impaired glucose tolerance is considered to be an early manifestation of diabetes and can be defined as pre-diabetes.Insulin resistance is an important feature and a key factor in the development of Type 2 diabetes.The phenomenon that excess androgen can cause obesity and insulin resistance in female has aroused much concern.However,the impact of hyperandrogenism on glucose metabolism in male has not been paid much attention.Abuse of androgen is widespread in the nowadays society and becomes one of public-health concern.Thus,exploration of side effects caused by excessive androgen intake on male is urgently needed.In this study,we applied SD rats as an animal model to investigate the effect of long-term super-physiological level of androgen on glucose tolerance and insulin sensitivity.Learned from previous studies,we screened out the appropriate slow-releasing capsule and verified its effect in vivo by subcutaneous implantation in female SD rats.We found that the slow-releasing tube made of medical adhesive(slow-releasing tube ?)was much better than the one(slow releasing tube ?)sealed by wooden materials.Thus we established the appropriate modeling method.Then we constructed a high blood DHT male rat model,and for the first time demonstrated that long-term(3 months,3 m)super-physiological concentration DHT could lead to glucose intolerance in male SD rats.Meanwhile,the results of insulin tolerance test and primary islets treatment indicated that pancreatic ?-cell dysfunction caused by DHT indirectly was responsible for the impaired glucose tolerance.In summary,the long-term(3 m)super-physiological concentration of DHT could cause impaired glucose tolerance and pancreatic ?-cell dysfunction in male SD rats.Our study will contribute to deepen people's understanding of the adverse effects of androgen and play a vigilant role for androgen abusers.