Protective Effects Of Estradiol And Resveratrol With Different Concentrations On Streptozotocin-induced Type-one Diabetes Female Mice

Objective:Diabetes incidence has been rising obviously in postmenopausal women.The animal experiments indicate that there is a higher prevalence rate of diabetes mellitus in male animals than in female animals.After testicle-removing operation,the probability of getting diabetes mellitus becomes lower in the operated male animals than in the non-operated animals;besides,the probability to get diabetes mellitus in ovariectomized female animals has also been higher than in the female animals with sham operation.The decreasing serum-estrogen level could induce the insulin resistance(IR),which is considered to be the real reason that leads to the increasing prevalence rate of diabetes mellitus.So,the estrogen replacement therapy has been thought to be a good way to administrate in clinical studies.It has always been known that estrogens can increase the body sensitivity to the insulin,improve glucose and lipid metabolism.Recently,more and more researches have shown that the estrogen can also act on islet cells,it can increase the secretion of insulin and one of the main usages could be protecting the islet cells from apoptosis.Nowadays,researchers have different opinions to the estrogen replacement therapy,they believe that it is harmful to use the estrogen for a long period,even during the process of estrogen replacement therapy.There are still some questions in debate about the type,dose,method of use,drug combination of the estrogen in the estrogen replacement therapy.The present studies were to investigate the effects of 17?-estradiol(Est)and resveratrol(Res)with different concentrations on fasting weight,fasting blood,plasma total antioxidant capacity,fasting insulin level of streptozotocin-induced type-one diabetes female mice,and to investigate the protective effects of estrogen and resveratrol(Res)with different concentrations on pancreatic islet cells of streptozotocin-induced type-one diabetes female mice.Methods:Female mice were randomly divided into ten treatment groups:Sham operation group ShamOvariectomy group OvxSham operation group and intraperitoneally injection of STZ Sham+STZOvariectomy group and intraperitoneally injection of STZ Ovx+STZOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Est 0.01 subcutaneous injection of 0.01 mg/kg 17(3-estradiolOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Est 0.1 subcutaneous injection of 0.1 mg/kg 17?-estradiolOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Est 1.0 subcutaneous injection of 1.0 mg/kg 17?-estradiolOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Res 0.1 subcutaneous injection of 0.1 mg/kg ResveratrolOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Res 1.0 subcutaneous injection of 1.0 mg/kg ResveratrolOvariectomy group and intraperitoneally injection of STZ and Ovx+ STZ +Res 10.0 subcutaneous injection of 10.0 mg/kg ResveratrolAll mice were received operation.The abdomen of all mice was opened along the abdominal mid line,and the ovarian of both sides was removed except the mice of sham group,then sutured the wound.All mice were allowed to recover for one week.One week later,all the groups were intraperitoneally injected STZ at every day lasting for five days.At the same time 17 ?-estradiol and resveratrol were administrated subcutaneously at every other day for 4 weeks.Blood glucose levels were measured once a week.T-AOC(total antioxidative capacity)was determined by colorimetry;MDA(malondialdehyde)was determined by TBA colorimetric method;serum insulin levels were determined with Radioimmunoassay.Results:1.The effects of endogenous estrogen on streptozotocin-induced type-one diabetes female miceBy tracking measurement,it was found that the decrease of endogenous estrogen level would significantly improve body weight and blood glucose of diabetic mice,and caused a decrease of plasma total antioxidant capacity and an increase of plasma malondialdehyde.After STZ treatment,the islet became smaller and the shape was deformed,the number of the islet beta-cells were significantly decreased.Compared with the Sham+STZ group,the islet beta-cell of Ovx+STZ group became smaller,and the serum insulin levels were decreased significantly.2.The effects of exogenous 17(3-estradiol(Est)with different concentrations on streptozotocin-induced type-one diabetes female miceEstradiol(0.1 mg/kg body weight)and(1.0 mg/kg body weight)significantly inhibited the increase of the blood glucose level which induced by in.jection of STZ,and significantly inhibited the rise of plasma malondialdehyde,and also improved the levels of plasma total antioxidant capacity and serum insulin.The 0.1 mg/kg and 1.0 mg/kg 17?-estradiol had protective effect on the islet,and the 0.1 mg/kg 17?-estradiol showed a best protection,while 0.01 mg/kg 17?-estradiol had no obvious effects.3.The effects of resveratrol(Res)with different concentrations on streptozotocin-induced type-one diabetes female miceResveratrol(10.0 mg/kg body weight)significantly inhibited the increase of the blood glucose level which induced by injection of STZ,and significantly inhibited the rise of plasma malondialdehyde.and also improved the levels of plasma total antioxidant capacity and serum insulin.Resveratrol(10.0 mg/kg body weight)had protective effects on the islet,while 0.1 mg/kg and 1.0 mg/kg resveratrol did not show protection.Conclusion:1.Endogenous estrogen and exogenous estrogen have protective effects on streptozotocin-induced type-one diabetes female mice.They can significantly inhibite the increasing of the blood glucose level,improve the level of plasma total antioxidant capacity and serum insulin,have protective effect on the islet.17?-estrogen(0.1 mg/kg)administration could make the plasma estrogen close to physiological level and has best protective effect.2.Resveratrol(10.0 mg/kg)administration subcutaneously has the same effects as 17P-estrogen(0.1 mg/kg),can significantly inhibit the increasing of the blood glucose level,improve the level of plasma total antioxidant capacity and serum insulin,and has some degree protective effects on streptozotocin-induced type-one diabetes female mice.The resveratrol might be therapeutic drug for diabetes mellitus.