The Effect Of Vitamin D On Diabetic Mice Exposed To Low Dose Cadmium

Objective: To investigate the influence of low dose cadmium exposure on experimental diabetic mice and the effect of vitamin D injection on diabetic mice exposed to low dose cadmium.The study results may provide theorical basis for the application of vitamin D in the prevention and treatment of cadmium poisoning among diabetic patients.Methods: This project is divided into three parts.(1)40 male C57BL/6 mice,aged 8 weeks,were randomly divided into 2 groups equally,including control group and streptozotocin(STZ)injected group.After consecutive intraperitoneal injection of STZ for 5 days(injection dose: 40 mg per kilogram of body weight),mices with fasting blood glucose(FBG)?11.1mmol/L were randomly assigned to diabetic model group(DM)and diabetic model with cadmium exposure group(DM+Cd)equally.The mice without STZ injection were randomly assigned to vehicle control group(Con)and cadmium chloride exposure group(Cd)equally.Then Cd and DM+Cd were exposed to cadmium chloride for 4 weeks.Heart,liver,lung,kidney,spleen,femurs and lumbar vertebraes of the mice were collected at the endpoint.The ratio of organ coefficient was calculated,and the three-dimensional reconstruction of femur and 5th lumbar vertebrae was analyzed after Micro-CT(Sky Scan 1174v2)scanning.(2)There were 64 male C57BL/6 mice,aged 8 weeks,in total at first.44 mice were selected randomly as STZ injected group.After consecutive intraperitoneal injection of STZ for 5 days(injection dose: 40 mg per kilogram of body weight),30 mice with FBG ?11.1mmol/L were randomly assigned to three groups equally,including diabetic model group(DM),diabetic model with cadmium exposure group(DM+Cd)and diabetic model with cadmium exposure and vitamin D supplementation group(DM+Cd+VD).The mice without STZ injection were assigned to vehicle control group(Con),cadmium chloride exposure group(Cd)and vitamin D supplementation group(VD)randomly.Then Cd,DM+Cd and DM+Cd+VD were exposed to cadmium chloride for 16 weeks.In order to investigate the effect of vitamin D on diabetic mice under cadmium exposure,mice in DM,DM+Cd and DM+Cd+VD groups were selected for subsequent experiments.Heart,liver,spleen,lung and kidney of the mice were taken at week 16 to calculate the ratio of organ coefficient.We also use Micro-CT to scan and reconstruct the three-dimensional structure of femur and 5th lumbar vertebrae.A week before the mice were executed,introperitoneal glucose tolerance test and insulin tolerance test were performed.(3)In the third part,original articles published before December 2017 were discovered through China National Knowledge Infrastructure.The searching keywords were as follows: vitamin D,diabetes.Endnote 7 software was used to eliminate duplicated publications and to analyze the data.Results:(1)FBG and body weight of mice increased steadily after a week of STZ injection.The FBG in diabetic mice with or without cadmium exposure was significantly higher than that in Con.The liver,spleen and kidney organ coefficients were higher in Cd and DM+Cd than in Con.Moreover,compared with Con,the trabecular number of femoral cancellous bone in DM+Cd was reduced,and trabecular thickness of trabecular bone was decreased and the arrangement was sparse.Trabecular number of femoral trabecular bone was also decreased in Cd and DM.These results showed that the trabecular bone was lost,trabecular separation was widened,the bone mineral density decreased and the structural degeneration was serious.However,for mice in four groups,these changes were not found in the fifth lumar spine.(2)The mice in Con had smooth fur and good spirits,STZ-injected group were relatively poor when establishing diabetic model.The mice fur in VD was superior to that of other groups during the period of cadmium exposure.There were significant difference between Con and STZ-injected group regarding bodyweight and FBG.FBG was increased in DM,DM+Cd,DM+Cd+VD compared with the Con during the period of cadmium exposure.The area under the curve(AUC)value did not differed significantly among DM,DM+Cd,DM+Cd+VD after intraperitoneal glucose tolerance tests(IPGTT).Additionally,insulin tolerance test results indicated that vitamin D intervention did not improve insulin resistance.However,we found that the length of left femur in DM+Cd was significantly lower than in DM and the thickness of trabecular of the fifth lumar spine had a significant difference between DM and DM+Cd,while these situation was effectively improved in DM+Cd+VD(P < 0.05).But vitamin D did not improve the higher spleen coefficient and hyperglycemia in diabetic mice with cadmium exposure.(3)By the end of 2017,the literatures on the relationship between type 2 diabetes mellitus and vitamin D in China showed an increasing trend.In total,47 articles were collected and 45 literatures(95.47%)were published in 2010-2017.47 articles were distributed in 40 different periodicals,most of which are in the field of public health.Nearly 42% of the articles are included in core periodicals.29.79% of the research articles are supported by relevant funds.The rate of author's cooperation was 91.49%,which was completed by 20 regions.93.62% of the research literatures were conducted in hospitals.Conclusion:1.Cadmium exposure has led to the reduction in bone density and microstructural changes in the femoral bone of the diabetic mice.However,no effect of cadmium exposure on the femur cortical bone and the lumbar vertebra cancellous bone in diabetic mice was observed.2.Vitamin D has no significant effect on glucose metabolism in diabetic mice with cadmium exposure.However,it has a slight positive regulatory effect on bone metabolism.Further studies are needed to investigate both specific roles and mechanisms.