To Investigate The Effect And Mechanism Of Aluminum Exposure On Glucose Metabolism And Mechanism Based On Pancreatic ? Cell Function And Insulin Resistance

Objective:The effects of aluminum exposure on glucose metabolism in rats were studied by establishing the aluminum exposure rat model,and its possible mechanism was discussed based on the function of islet?cells and insulin resistance.Methods:Totally 60 healthy Wistar male rats were randomly divided into 4 groups:the control group?C group?,the low dose group?L group?,the middle dose group?M group?and the high dose group?H group?,15 rats in each group.The rats model of control group received intraperitoneal normal saline.The rats model of aluminum exposure was established by intraperitoneal injected different dosages AlCl₃ solution at?2,4 and 8 mg/kg,d?.This experiment lasted for 30 days.On the 10th,20th and 30th day,5 rats in each group were taken to detect the relevant indexes.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 with homeostasis model assessment?HOMA?.Pancreatic tissue was taken for pathological examination.The activity of serum adenosine triphosphatase was detected by spectrophotometry.Glucose transporter 4?GLUT4?expression in skeletal muscle and adipose tissue was detected by quantitative PCR and Western blot.Results:1.Compared with the control groups,FBG level of 10th,20th and 30th day in M and H group at the same time point were higher,difference was statistically significant?P<0.05?;FINS level of 10th and 20th day in H group at the same time point were higher than those in C group,but lower on the 30th day than those in C group,difference was statistically significant?P<0.05?;HOMA-IR level of 20th day in M and H group were higher than those in the C group,and the level of 30th day in L and M group were higher than those in the C group,difference was statistically significant?P<0.05?;HOMA-?level of 20th and30th in M and H groups were lower than those of C group,difference was statistically significant?P<0.05?.2.Pathology showed that pancreatic damage changed more profoundly with the increasement of Al concentration and treatment time in each dose group.In C group,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 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.The effect of aluminum on the ATPase activity of rats in each group:The level of Na⁺-K⁺-ATPase at the same time point in M and H group were lower than those in C group?P<0.05?;Ca²⁺-Mg²⁺-ATPase in H group at the same time point was lower than those in C group,difference was statistically significant?P<0.05?.4.Effects of Aluminum on GLUT4 mRNA Expression:?1?Skeletal Muscle Tissue:The GLUT4 mRNA level of 10th day in H group was significantly lower than that of C group?P<0.05?,the GLUT4 mRNA level of 20th and 30th day in L,M and H group at the same time point were significantly lower than those in C group,difference was statistically significant?P<0.05?;With the prolongation of aluminum exposure time,the GLUT4 mRNA level decreased in each dose groups.The expression in M and H group was significantly different at different time points?P<0.05?,and there was a time–response relationship.?2?Adipose tissue:On the30th day,the GLUT4 mRNA levels in each dose group were significantly lower than those in C group,difference was statistically significant?P<0.05?.There was no significant difference between each time point in each group?P>0.05?.5.Effects of Aluminum on GLUT4 protein expression?1?Skeletal muscle:On the 10th and 20th day,GLUT4 protein expression in M and H groups was significantly lower than that in C group?P<0.05?;on the 30th day,GLUT4protein expression in each dose group was significantly lower than that in C group?P<0.05?,and there was a dose-response relationship.With the prolongation of aluminum exposure time,the expression of GLUT4 protein in each dose group showed a decreasing trend:there were significant differences between various time points in both the L and H groups?P<0.05?,and there was a time–response relationship.?2?Adipose tissue:On the 30th day,the expression of GLUT4 protein in H group was significantly lower than that in C group?P<0.05?.The protein expression of L and H groups on the 30th day was significantly lower than that on the 10th day,difference was statistically significant?P<0.05?.Conclusion:?1?Aluminum exposure may lead to decreased?-cell function and abnormal glucose metabolism through damaging pancreatic tissues and reducing the activity of Ca²⁺-Mg²⁺-ATPase.?2?Aluminum exposure may reduce the ability of cells to transport glucose through down-regulating GLUT4 expression in skeletal muscle and its translocation-related ATPase activity,thus triggering insulin resistance,affecting blood glucose regulation,leading to glucose metabolism disorders.