| Backgroud Adiponection is a cytokine mainly secreted by adipose tissue and involves in glucolipid metabolism and insulin resistance(IR).The adiponectin deficinecy is related to a cluster of IR-related diseases,such as metabolic syndrome,diabetis mellitus,and non-alcoholic fatty liver disease(NAFLD).As one of the antigyperglycemic drugs,sitagliptin,a depeptidyl peptidase-4(DPP-4)inhibitors,stimulates the proliferation of pancreatic β cell,improves the reactivity of pancreatic islet β cell and insulin secretion,while inhibits the glucagon secretion and the production of endogenous glucose.Objective We aim to assessthe levelof adiponectin in serum,perirenal adipose,skeletal muscle and liver of obese diabetic rats.The effect of sitagliptin,on glucolipid metabolism and the expression of adiponectin is as well evaluated.Methods Sixty healthy male Sprague-Dawley(SD)rats were randomly allocated to high fat diet group(HD group,n=45)and normal control group(NC group,n=15).35 out of 45 HD rats developed obesity after 12 weeks.They were further stratified into positive control group withobesity(OB group,n=8)and streptozotocin(STZ)treated group(n=27).STZ was administrated via peritoneal injection at a dose of 35 mg/kg per day.20 out of 27 STZ treated rats eventually progressed to diabetes,half of which was subsequently medicated with Sitagliptin(SP group,n=10).The rest remained diabetes and untreated(DM group,n=10).The level of serum adiponection,total cholesterol(TCH),triglyceride(TG),low-density lipoprotein(LDL-C),fasting blood glucose(FBG),and fasting insulin(FINS)were measured before and after the intervention of Sitagliptin by ELISA.HOMA-β and HOMA-IR were later calculated based on FBG and FINS.Additionally,the expression of adiponectin in skeletal muscle,perirenal adipose and liver was detected by westernblotting in NC,DM and SP group respectively.Results 1.We established rat models with both obesity and diabetes.2.Biochemical indicators were compared in different groups:(1)Before the treatment of sitagliptin,the levels of BW,FINS,HOMA-IR,LDL-C were significantly higher in OB group than those in NC group,while the level of HOMA-β was lower(P<0.05)and the levels of FBG,TG,and TCH remained no difference.If compared with NC group,the levels of BW,FBG,FINS,HOMA-IR,TG,TCH,and LDL-C in DM group and SP group increased while the levels of HOMA-β decreased with a statistical significance(P<0.05).The differences of various parameters between DM group and SP group reached no statistical significance(P>0.05).(2)After the treatment of sitagliptin,the levels of FBG and FINS in SP group elevated while the levels of HOMA-β declined significantly as compared with those in NC group(P<0.05).The levels of FBG,TG,LDL-C,FINS and HOMA-IR in SP group decreased while the levels of HOMA-β increased compared with those in DM group with a statistical significance(P<0.05).The level of BW in SP group decreased slightly compared with DM group(P>0.05).The levels of BW,FINS and HOMA-IR in SP group decreased compared with those in OB group with a statistical significance(P<0.05).3.The change of serum adiponectin levels(1)Before treatment with sitagliptin,the adiponectin levels in DM,SP and OB group significantly decreased compared with that in NC group(P<0.05),but statistical difference was not observed between SP group and DM group(P>0.05).(2)After treatment with sitagliptin,the adiponectin level in SP group increased compared with that in DM and OB group with a statistical significance(P<0.05),but there was no statistical significance between SP and NC group(P>0.05).The level of adiponection in OB group was statistically different compared with NC group and SP group(P<0.05),but was similiar as DM group(P>0.05).4.The change of adiponectin expression in different tissues: Adiponectin expressionin perirenal adipose of DM and SP group was lower than that in NC group(P<0.05),which were also observed in liver tissue and muscular tissue.Adiponectin expression in liver tissue in SP group was higher than that of the DM group,which was also observed in muscular tissue(P<0.05),adiponectin expression levels in perirenal adipose of SP group was higher than that of the DM group,but there was no significant difference between two groups(P>0.05).5.Pearson correlation analysis showed that adiponectin was independently related to BW,TG,TC,LDL-C,FBG,FINS,HOMA-IR and HOMA-β after treatment with sitagliptin(P<0.05).Conclusions The level of adiponectin in serum,perirenal adipose,skeletal muscle and liver tissue reduced in obese rats and obese diabetic rats as compared to healthy controls.Sitagliptin intervention can improve the glucolipid metabolism,increase serum adiponectin levels in obese diabetic rats and improve the adiponection protein expression levels in muscular tissue and liver tissue.Background A large number of studies at home and abroad have shown that the prevalence of malignancies,especially breast cancer,is significantly higher in women with diabetes mellitus,especially in obese patients.The exact mechanism is not clear so far.Recently,a number of studies have shown that abnormal adipokine secretion plays an important role in the occurrence and development of breast cancer.This study was designed to investigate the expressions of advanced glycation end products receptor(RAGE),G1 / S specific cell cycle protein(Cyclin D1)and nuclear transcription factor(NF-κB)in serum,breast cancer tissues and adjacent tissues in both diabetic breast cancer and non-diabetic breast cancer patients.The correlation between adiponectin and the above mentioned factors was also analyzed.The potential role of adponectin in the pathogenesis of type 2 diabetes is thereby warranted.Objective We aim to delineate the different levels of serum adponectin and different expressions of RAGE,Cyclin D1 and NF-κB in both breast cancer tissues per se and its adjacent tissues between breast cancer patients with and without type 2 diabetes mellitus.The correlation between adiponectin and the expression of above mentioned factors was also assessed.Accordingly,the pissible signaling pathway of adiponectin that invovled in the development of breast cancer in type 2 diabetic patients was concluded.This may provide a promising target for breast cancer patients with type 2 diabetes.Method Clinical data were collected and 5ml of venous blood was collected for detecting serum cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),Low density lipoprotein(LDL),fasting blood glucose(FBG),fasting insulin(FINS),total adiponectin,and high molecular weight adiponectin in 20 diabetic breast cancer patients and 30 non-diabetic breast cancer patients.HOMA-IR were thereby calculated.All the breast cancer tissues and normal breast tissues were collected during surgery.The breast tissues from different patients were stratified into four groups as follows: the breast cancer tissue specimen of the diabetic breast cancer patients(DBCC group),the normal breast tissue specimen of the diabetic breast cancer patients(DBCN group),the breast cancer tissues of non-diabetic breast cancer patients(BCC group),and the normal breast tissue specimen of the non-diabetic breast cancer patients(BCN group).The expression of RAGE,Cyclin D1 and NF-κB in tissue specimen were detected by Westernblotting and q RT-PCR in each group.Result 1.There was no significant difference of the age and body mass index between the diabetic breast cancer patients group and non-diabetic breast cancer patients group(P> 0.05),although the diabetic patients was marginally older.Futhermore,the tumor size was significantly different between the two groups(P <0.05),while neither tumor lymphatic metastasis nor distant metastasis between two groups reached significence(P> 0.05).2.Serum TG levels and HOMA-IR in diabetic breast cancer patients were significantly higher than those in the control group(P <0.05),and the levels of serum HDL,serum adiponectin and serum high molecular weight adiponectin in diabetic breast cancer patients were lower than those in non-diabetic breast cancer patients with diabetes(P <0.05).However,there was statistical difference in neither serum TC level nor serum LDL levels between two groups(P> 0.05).3.The correlation analysis showed that serum adiponectin level and serum high molecular weight adiponectin levels were negatively correlated with HOMA-IR(P <0.05),positively correlated with serum TG(P <0.05),but not relevant to BMI and serum HDL levels(P> 0.05).Spearman correlation analysis showed that serum adiponectin level and serum high molecular weight adiponectin level were negatively correlated with tumor size(P <0.05).4.The expression of RAGE protein in DBCC group was higher than that in BCC group and DBCN group(P <0.05).Meanwhile,the expression of RAGE protein in BCN group was significantly lower than that in DBCN group and BCC group(P <0.05).Westernblotting and q PCR were used to detect the expression of NF-κB and Cyclin D1 at the protein and m RNA level respectively.The results showed that the tranlational and transcriptional expression of both NF-κB and Cyclin D1 in DBCC group were higher than those in BCC group and DBCN group(P <0.05)and there was no significant difference between DBCN group and BCN group(P> 0.05).5.The expression of cyclin D1 was positively correlated with the expression of RAGE(R = 0.931,P <0.001),but the expression of NF-κB were not correlated with the expression of RAGE(P> 0.05).6.Pearson correlation analysis showed that serum adiponectin level was negatively correlated with the expression of RAGE,Cyclin D1 and NF-κB(P <0.05)Serum high molecular weight adiponectin level negatively correlated with the expression of both RAGE and NF-κB(P <0.05),but not with the expression of Cyclin D1(P> 0.05).7.The expression of Adiponectin in breast cancer tissue was negatively correlated with the expression of RAGE、NF-κB and Cyclin D1(P<0.05).Conclusion 1.The tumor stage is higher in diabetic breast cancer patients than non-diabetic breast cancer patients,and breast cancer with higher tumor stage progresses faster.2.Serum levels of HDL,adiponectin and high molecular weight adiponectin were lower in diabetic breast cancer patients as compared to non-diabetic breast cancer patients,which suggests that adiponectin may be a protective factor for breast cancer in diabetic patients.3.The expression of RAGE,Cyclin D1 and NF-κB in diabetic breast cancer patients were significantly higher than that in non-diabetic breast cancer patients,indicating that abnormal cell generation cycle maybe involved in the development of breast cancer.4.Serum adiponectin and high molecular weight adiponectin levels were negatively correlated with RAGE and NF-κB expression.The expression of Adiponectin in breast cancer tissue was negatively correlated with the expression of RAGE、NF-κB and Cyclin D1.Thus,it is proposed that adiponectin may regulate the development of breast cancer in diabetic patients by regulating RAGE-NF-κB signaling pathway. |
