Effects Of Aluminum Exposure On Glucose Metabolism And Its Mechanism Study

Part 1: The Clinical Study of Influence of Aluminum Exposure on Glucose Metabolism and Islet Cell Function.Objective: To observe the changes of glycometabolism and related indexes of islet cells in healthy population after aluminum exposure,and investigated the mechanisms of aluminum exposure on glycometabolism and islet beta cell function.Methods: 46 cases of West Aluminum Industrial Base residents?aluminum exposure group?and 48 healthy adult of Non Industrial residents|?control group?were detected body mass index?BMI?,systolic blood pressure?SBP?,diastolic blood pressure?DBP?,level of serum aluminum,fasting blood glucose?FPG?,fasting insulin?FINS?,glycosylated hemoglobin?Hb A1c?,triglyceride?TG?,high density lipoprotein?HDL-C?,low density lipoprotein?LDL-C?,creatinine?Cr?and calculated insulin resistance index?HOMA-IR?and pancreatic ? cell function index?HOMA-??.Results: The level of serum aluminum of the exposed group was significantly higher than that in control group,the difference was statistically significant?P<0.01?.The FBG and HOMA-IR in the exposed group was significantly higher than that in control group,the difference was statistically significant?P<0.05?.HOMA-? in the aluminum exposure group was significantly lower than the control group,the differences were statistically significant?P<0.01?.SBP in the aluminum exposure group was significantly higher than that in control group?P <0.05?.Conclusion:?1?Long-term aluminum exposure may lead to glucose metabolismdisorders by accelerating insulin resistance and reducing insulin secretion.?2?Long-term aluminum exposure can elevate blood pressure.Part 2: Effects of Aluminum Exposure on Rats Pancreatic Cells and PI3K Expression.Objective: We research the effect of aluminum exposure on the morphology of islet cells and expression of phosphatidylinositol 3 kinase?PI3K?by establishing a rat model of aluminum exposure and to explore the mechanism of the disorder of glucose metabolism caused by aluminum exposure.Methods: Totally 40 healthy Wistar male rats were randomly divided into 4 groups:the control group,the low dose group,the middle dose group and the high dose group,10 rats in each group.The rats model of control group received intraperitoneal normal saline.According to the literature modeling method,the rats model of aluminum exposure was established by intraperitoneal injected different dosages Al Cl₃ solution at?2,4 and 8 mg/ kg,d?.This experiment lasted for 4 weeks.Fasting Blood-glucose?FBG?and Serum levels of insulin?FINS?were measured.The insulin resistance index?HOMA-IR?and pancreatic ? cell function index?HOMA-??were calculated and analyzed.Pancreatic tissue was taken for pathological examination.PI3 K expression in skeletal muscle and liver tissue was detected by quantitative PCR and immunohistochemical.Results: 1.The levels of FBG in low,medium and high dose aluminum exposure groups were significantly higher than those in control group,difference was statistically significant?P<0.01?.The level of FINS secretion in low and middle dosage groups was significantly higher than that in control group,but it lower than control group in high dose group,difference was statistically significant?P<0.01?;The levels of HOMA-IR in the low and middle dose groups were significantly higher than those in the control group,but in the low and middle dose groups,the levels of HOMA-IR were significantly lower than those in the middle dose group,difference was statistically significant?P<0.01?;In low,medium and high doses groups,the level of HOMA-? was significantly lower than that of the control group, and the difference was statistically significant?P<0.01?.2.The results of HE staining showed that the structures of pancreatic acinus and islets were complete and the edge was clear.Islet cells were closely arranged and evenly distributed,displaying round or oval cell clusters in control group.In Aluminum exposure groups,there was pancreatic tissue congestion,pancreatic acini expansion and congestion,with disordered islet cell arrangement,as well as significant reduction in cell number.In addition,there were vacuolar changes and nuclear condensation suggesting necrotic lesions.3.Effects of Aluminum on PI3 K protein expression:the expression of PI3 K protein in liver and skeletal muscle decreased with the increase of aluminum dose.The expression of PI3 K protein in each dose group was significantly lower than that in control group,difference was statistically significant?P<0.01?.4.Effects of Aluminum on PI3 K m RNA Expression:?1?Liver tissue: Compared with control group,the relative expression of PI3 K m RNA in middle and high dose aluminum exposure group was significantly decreased,difference was statistically significant?P<0.05?;Compared with low dose group,the expression of PI3 K m RNA in high dose group was significantly decreased,difference was statistically significant?P<0.01?.?2?Skeletal Muscle Tissue: Compared with control group,the relative expression of PI3 K m RNA in medium and high dose aluminum exposure groups was significantly decreased?P<0.01?;Compared with the low dose group,the expression of PI3 K m RNA in medium and high dose groups was significantly decreased,difference was statistically significant?P<0.01?.Conclusion: Exposure to aluminum can lead to the destruction of islet cells,decreased insulin secretion,decreased expression of PI3 K,and insulin resistance,which may be one of the mechanisms for the disorder of glucose metabolism.