| Objective: Diabetes Mellitus (DM) and Osteoporosis (OP) are bothchronic metabolic diseases. Various complications could be triggered with theextension of the course of disease, thus seriously affecting people’s life qualityand causing huge economic damages to the society. As the life expectancy hasbeen increased in general, the morbidity of these two diseases is on the rise. Inrecent years, GLP-1and its signal pathway’s role in the treatment of DM hasreceived wide attention. GLP-1generates insulin for the glucose-dependentpancreas and inhibits insulin secretion. It could reduce food intake dose andbody weight by stimulating vagus nerves and center receptors, and regulateblood sugar by slowing down the speed of gastic emptying. The study on theeffects of GLP-1on bone metabolism has become a research hotspot in recentyears. Research has shown that the GLP-1receptor is pro-osteoblast. The ratsdevelop OP when the GLP-1receptor is knocked off. It is found that there iscertain interaction between DM and OP, but no report has been found onwhether they have common pathogenesis. This study compares the differencesin liver GLP-1receptor and PKA among the normal control group, type2diabetic rats group, rats under ovariectomy group and type2diabetic ratsunder ovariectomy group, in order to find out whether there is a corelationbetween the pathogenesis/development of DM and OP and the GLP-1receptor/PKA signal pathway, and illustrate whether DM and OP have somecommon GLP-1related pathogenesis.Methods:100Wistar rats were randomly divided into four groups after1week feeding: normal control group(NC,N=24), type2diabetes control group(DC,N=24),ovariectomy group(NOVX,N=26), type2diabetic rats under ovariectomy group (DOVX,N=26). The weight of rats in the four groups had nosignificant difference. NC and NOVX groups were fed with normal feedstuff while DC and DOVX groups were fed with high-sugar-fat feedstuff,T2DM were made by intraperitoneal injection of STZ.Rats chosen for NOVXand DOVX group were ovariectomied under anesthesia1week later after T2DM model were done. Body weight, bone mineral density(BMD),fasting bloodglucose level(FBG) and fasting insulin level(INS) were measured at0week,4weeks,8weeks and12weeks after the operation. At4weeks,8weeks,12weeks after ovariectomy, four rats were randomly executed, the livers of which were separated after anesthesia. The expression of GLP-1R and PKA at protein level was detected by IHS (immunohistochemistry). The experimental data was presented as mean±standard deviation. Variance Analysis were used tocheck differences between groups by SPSS13.0,P<0.05was considered statistically significant.Results:1Body weight of rats in each group: There were no differences found betweenthe4groups right after ovariectomy (0week). The body weight of NOVXgroup is significantly higher than the other three groups; the body weight ofDC group is significantly lower than the other three groups.2Bone mineral density (BMD): There is no significant difference betweengroups at4weeks after ovariectomy, but at8weeks,12weeks afterovariectomy, the BMD of NOVX group is significantly lower than NC group,the BMD of DOVX group is significantly lower than DC group. With theprogression of the experiment, the BMD of OVX groups declines. The BMDof DOVX group declines most obviously, followed by NOVX group.3The comparison of serum markers3.1Fasting plasma glucose (FBG): After STZ were injected one week, theFBG level in DC group and DOVX group are significantly higher than that inNC and NOVX groups which indicate that the T2DM rat model issuccessfully established. At4weeks,12weeks after ovariectomy, the FBG inDOVX group is much higher than other three groups; At8weeks afterovariectomy, the FBG of DC and DOVX group is significantly higher thanNC group. 3.2Insulin level (INS): The INS of diabetic group (DC group and DOVXgroup) rats is significantly higher than non-diabetic group (NC group andNOVX group) rats at each period, but there is no statistical differencesbetween DC group and DOVX group, NC group and NOVX group.4The expression of GLP-1RImmunohistochemistry results: GLP-1R expression is located incytomembrane and cytoplasm of the hepatocyte. At4weeks after ovariectomy,the expression of GLP-1R in DOVX group is the highest，followed by DC,NOVX, NC groups. There were no differences found between DC group andNOVX group, the same with NC group and NOVX group. At8weeks afterovariectomy, the expression in NC group is much lower than DC, DOVX,NOVX groups. There were no differences found between DC, DOVX, NOVXgroups. At12weeks after ovariectomy, there were no differences foundbetween the4groups. In NC group, the expression of GLP-1R at4weeksafter ovariectomy is lower than8weeks, the expression of GLP-1R at8weeksand12weeks have no differences. In NOVX group, the expression ofGLP-1R at8weeks after ovariectomy is much higher than4weeks and12weeks, the expression of GLP-1R at4weeks and12weeks have no differences.In DC group, the expression of GLP-1R at12weeks after ovariectomy ismuch lower than4weeks and8weeks, the expression of GLP-1R at4weeksand8weeks have no differences. In DOVX group, the expression of GLP-1Rat12weeks after ovariectomy is much lower than4weeks and8weeks, theexpression of GLP-1R at4weeks and8weeks have no differences.5The expression of PKAImmunohistochemistry results: PKA expression is located in cytoplasmof the hepatocyte. At4weeks after ovariectomy, the expression of PKA inDOVX group is the highest，followed by DC, NOVX, NC groups. There wereno differences found between DC group and NOVX group. At8weeks afterovariectomy, the expression in NC group is much lower than DC, DOVX,NOVX groups. There were differences found between DC, DOVX, NOVXgroups. At12weeks after ovariectomy, the expression in DC group is much higher than NC, DOVX, NOVX groups. There were no differences foundbetween NC, DOVX, NOVX groups. In NC group, the expression of PKA at12weeks after ovariectomy is higher than8weeks, the expression of PKA at8weeks and4weeks have no differences. In NOVX group, the expression ofPKA at12weeks after ovariectomy is much lower than4weeks and8weeks,the expression of PKA at4weeks and8weeks have no differences. In DCgroup, the expression of PKA at8weeks after ovariectomy is much higherthan4weeks and12weeks, the expression of PKA at4weeks and12weekshave no differences. In DOVX group, the expression of PKA at4weeks afterovariectomy is the highest，followed by12weeks and8weeks. There weredifferences found between the three time groups.Conclusions:1At the same time, the expression of GLP-1R and PKA of diabetic ratswere higher than control groups. It could be considered that diabetes couldaffect the expression of GLP-1R and PKA in the hepatocyte.2As the extension of time, the expression of GLP-1R of DC and DOVXgroups were lower than before.3The expression of GLP-1R in DOVX groups is higher than in DCgroups at4weeks. It could be considered that osteoporosis could affect theexpression of GLP-1R in the hepatocyte.4The trends of PKA and GLP-1R level are not entirely consistent. PKAis a indicate target protein exist in many signal transductions. Its expression isinfluenced by various factors. It has some localization as an observation targetin the GLP-1signaling pathway.5The intrinsic relationship between type2diabetes and osteoporosisremains to be further discussed. |
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