Uncarboxylated Osteocalcin Of Fluorine To The Regulation Of Glucose Metabolism Disorder

The chapter ?:The effects of excessive fluoride on the body of the osteocalcin content and glucose metabolism Objective:Discussed different doses fluoride acting on the body after the osteocalcin and glucose metabolism.Methods:1.Select 65 cases diagnosed as skeletal fluorosis patients were skeletal fluorosis group,the other 65 patients who had no bone disease and excluded from are interrelated skeleto disease were control group.Record the general condition,calculate body mass index(BMI),Enzyme-linked immunosorbent assay(ELISA)serum total Osteocalcin(t OCN),uncarboxylated Osteocalcin(uc OCN),Fasting insulin(FINS)content,determination of blood glucose(GLU)and glycosylated serum protein(GSP)by chemical method.Calculated Insulin resistance index(HOMA-IR).2.8-24 g 36 male C57 mice were divided into 3 groups,intervented by 0 mg/L,100 mg/L,150 mg/LNa F,the detected of body mass after 2,4,6,8,10,12 W.12 W after the content of blood glucose and glycosylated hemoglobin(Hb A1c)was detected by chemiluminescence method,and the contents of t OCN,uc OCN,FINS and glucagon were detected by ELISA.Pathological changes of pancreas were observed by Hematoxylin-Eosin(HE)staining,Immunohistochemical detection of pancreas the expression of Osteocalcin(OCN),cyclin D2.Results:1.Compared with the control group,the uc OCN,FINS and GSP were significantly higher(P<0.05).t OCN and HOMA-IR in skeletal fluorosis group were higher than those in control group,but there was no statistical significance(P>0.05).GLU in fluorosis group was lower than that in control group but there was no statistical significance(P>0.05).Correlation analysis showed that uc OCN was positively correlated with FINS(P<0.05).uc OCN was negatively correlated with GLU and HOMA-IR(P<0.05),and uc OCN was not correlated with BMI,t OCN,GSP(P>0.05).2.(1)There were significant differences in t OCN and uc OCN between the groups of fluorosis(F=32.31,17.41,P<0.05).The t OCN and uc OCN in each group of fluorosis were higher than those in control group.The difference of GLU between the two groups was statistically significant(F=22.75,P<0.05),and the GLU in each group of fluorosis was higher than that of the control group.The difference of Hb A1 c,Glucagon and FINS between the two groups was statistically significant(F=102.40,73.61,5.32,P<0.05),and the Hb A1 c and FINS in each group of fluorosis was higher than that of the control group,The content of Glucagon in each group of fluorosis was lower than that in control group.uc OCN was positively correlated with t OCN and FINS,and negatively correlated with GLU and Hb A1 c,and no correlation with Glucagon.(2)Pathological examination showed that the shape of the acinar cells in the 150mg/L group was irregular,with a small number of cell boundaries slightly blurred,partial islet cell nuclei becomed less and the distribution was sparse.(3)The expression of OCN in the pancreas of the fluoride group was negative,and the expression of Cylin D2 was positive.Conclusion:1.Excessive fluoride can lead to significant increase of serum uc OCN in patients with skeletal fluorosis and mice,which is characterized by bone proliferation.2.Excessive fluoride can cause the disorder of glucose metabolism in patients with skeletal fluorosis,which is characterized by abnormal glucose metabolism.3.The effect of excessive fluoride on uc OCN and FINS.The chapter?:Effects of different doses of fluoride on pancreatic islet beta cell function in vitro Objective:To observed the effects of different doses of sodium fluoride(Na F)on the proliferation of pancreatic islet beta cells and the secretion of insulin(Insulin,INS)in vitro.Methods:0,0.1,0.5,1,2,4,16 mg/LNa F respectively intervention mice islet Beta-TC-6 cells of 24 h,48 h,72 h,96 h,HE staining was used to observe the cell morphology,4,5-Dimethyl-2-Thiazolyl-2,5-Diphenyl-2-H-Tetrazolium Bromide(MTT)colorimetric assay was used to detect the cell proliferation activity;Determination of insulin secretion by ELISA.Results: 0.5 mg/L,1.0mg/LNa F 72 h,the islet beta cell proliferation and insulin secretion were markedly increased compared to control group.(P(27)0.05);More than 8 mg/L with the increase of Na F dosage and treatment time,cell proliferation and insulin secretion was significantly reduced(P(27)0.05),And the cells grew slowly,the number decreased,not easy to adhere to the wall or fused into pieces,mostly oval or round cells.Conclusion:Low dose of Na F can promote the proliferation and insulin secretion of pancreatic islet beta cells.With the increase of dose and time,the inhibition of Na F on cell proliferation and insulin secretion was enhanced.The chapter?:Effects of excessive fluoride on the function of pancreatic islet beta cells in vitro after blocking uc OCN-GPRC6 A pathway Objective : After blocking the uc OCN-GPRC6 A pathway,To observe the effects of excessive fluoride on INS secretion and proliferation of mouse pancreatic islet Beta-TC-6 cells in vitro.To investigated the effect of fluoride on the function of pancreatic islet beta cells by uc OCN-GPRC6 A pathway.Methods: The uc OCN-GPRC6 A pathway was chosen to block and block the islet Beta-TC-6 cells of the two groups,8 mg/LNa F,150 mmol/Luc OCN,8 mg/LNa F+150 mmol/Luc OCN intervention 48 h,ELISA method was used to measure the content of INS,the total RNA and protein were extracted,and the expression of Cyclin D1 and Cyclin D2 were detected by RT-PCR and Western blot.Results: Non transfection: the secretion of INS and the expression of Cyclin D1,Cyclin D2 m RNA,protein of Na F group were significantly lower than those in the control group(P(27)0.05),In the uc OCN group,the levels of INS,Cyclin D1,Cyclin D2 m RNA and protein were higher than those in the blank group(P(27)0.05),In the Na F+uc OCN group,the levels of INS,Cyclin D1,Cyclin D2 m RNA and protein were lower than those in the blank group and the uc OCN group,which was higher than that in the Na F group(P(27)0.05).Transfection: there was no statistically singnificant in the levels of INS secretion,Cyclin D1,Cyclin D2 m RNA and protein in the uc OCN group compared with the blank group,The Na F+uc OCN group of INS secretion,the expression of Cyclin D1,Cyclin D2 m RNA and protein reduce than control group(P(27)0.05),Na F treated group showed no statistically singnificant.Comparison between the two groups: non transfected uc OCN group INS levels and the expression of Cyclin D1,Cyclin D2 m RNA and protein increased significantly than transfected uc OCN group(P(27)0.05).Non transfected Na F+uc OCN group compared with the transfected Na F+uc OCN group INS secretion,the expression of Cyclin D1,Cyclin D2 m RNA and protein were significantly increased(P(27)0.05),Non transfection blank group,Na F exposure group the levels of INS and the expression of Cyclin D1,Cyclin D2 m RNA,protein was no statistically singnificant with transfection blank group,Na F exposure group.Conclusion:1.uc OCN can reduce the damage effect of excessive fluoride on pancreatic islet cells.2.Fluorine can act on islet cells through uc OCN-GPRC6 A pathway.