Objective To investigate the effects of liraglutide on gene expression related to cholesterol metabolism in ApoE-/-mice with adiponectin deficiency. Methods Thirty six ApoE-/-mice fed with the high-fat diet were subdivided into four groups. One group was given 100 μl(1×109PFU) of adenoviral pAd-U6-GFP(GFP group, n=6). The second group received 100 μl of adenoviral pAd-U6-Acrp30(ADI group, n=10). The third group was given 100 μl of adenoviral pAd-U6-Acrp30 and liraglutide(HEA group, n=10) and the fourth group was given only 100 μl sterile saline(HF group, n=10). Insulin sensitivity and glucose metabolism were assessed by the hyperinsulinemic-euglycemic clamp technique using 3-[3H] glucose as a tracer. Plasma adiponectin level was evaluated using a commercially available ELISA kit. The mRNA expressions of genes involved in cholesterol metabolism were measured by quantitative realtime PCR. Results Fasting blood glucose(FBG), free fatty acids(FFA), total cholesterol, triglyceride, low density lipoprotein cholesterol, adiponectin, and fasting plasma insulin(FINS) in ADI mice were significantly higher than those in the other groups(P＜0.01), while high density lipoprotein cholesterol was significantly lower(P＜0.05). During the clamp, glucose infusion rate(GIR) in ADI group was significantly lower than the other groups(P＜0.01), and hepatic glucose production(HGP) significantly higher in ADI group(P＜0.01). The mRNA expressions of INSIG2 and LDLR in ADI group were significantly down-regulated in HEA group(P＜0.01 or P＜0.05), while HMGCR and SREBP-2 were significantly up-regulated in HEA group(P＜0.01 or P＜0.05). Conclusions Liraglutide regulates a number of genes involved in cholesterol metabolism and ameliorates hypercholesterolemia by elevating plasma adiponectin level.

Objective To analyze the correlation between triglyceride glucose index (TyG) combined with different obesity indexes and new-onset ischemic stroke (IS) in 10 years in prediabetes population in Luzhou,Sichuan through cohort study. Methods A total of 2551 residents who participated in the epidemiological survey in Luzhou in 2011 and were diagnosed as having prediabetes were enrolled. According to the quartiles of baseline TyG-waist circumference (WC),TyG-waist to height ratio (WtHR),TyG-body mass index (BMI),and TyG-waist to hip ratio (WHR),they were divided into the 1st,2nd,3rd,and 4th quartiles groups (Q1,Q2,Q3,and Q4 groups). The incidence of new-onset IS in each group in 10 years was analyzed. The relationships between TyG-WC,TyG-WtHR,TyG-WHR and new-onset IS were analyzed by multivariate logistic regression. Results Among the 2551 prediabetes subjects enrolled in the study,123 died of various causes during the 10 years of non-intervention follow-up,with a mortality of 4.8％;142 had new-onset IS,with an incidence of 5.6％;and 224 had new-onset diabetes mellitus,including 22 also had new-onset IS,accounting for 9.8％. The quartile grouping analyses of TyG-WC and TyG-WtHR showed that the incidence of new-onset IS in prediabetes subjects over 10 years was Q4 group>Q3 group>Q2 group>Q1 group,with significant differences (P<0.05). The quartile grouping analysis of TyG-BMI showed that there was no significant difference in the incidence of new-onset IS (P>0.05). The quartile grouping analysis of TyG-WHR showed that the incidence of new-onset IS was Q3 group>Q4 group>Q2 group>Q1 group,with significant difference (P<0.05). Multivariate logistic regression analysis showed that TyG-WtHR was associated with new-onset IS in prediabetes subjects,either without adjusting any variable or after adjusting multiple factors. Conclusion TyG-WtHR is a risk factor of IS in prediabetes individuals. Enhancing management of prediabetes patients with high TyG-WtHR may reduce the risk of IS.

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

OBJECTIVE: To explore the relationship between serum cystatin-C (Cys-c) levels and vibrating perception threshold (VPT) in patients with Type 2 diabetes mellitus (T2DM).
 METHODS: According to the symptoms, signs and results of lab examination, a total of 352 patients with T2DM were divided into a diabetic peripheral neuropathy group (DPN group, n=107) and a non-diabetic peripheral neuropathy group (NDPN group, n=245). Serum Cys-c levels were measured by radioimmunoassay method. The relationship between serum Cys-c levels and VPT, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), glucose and blood pressure and other parameters were also analyzed by correlation and multiple regression analysis. All T2DM patients were divided into a high Cys-c levels group (n=89) and a low Cys-c levels group (n=263) according to the upper quartile of Cys-c, and the incidence of DPN and VPT levels in each group were compared. Risk factors of DPN in T2DM patients were analyzed by binary logistic regression analysis and receiver operating characteristic (ROC) curve was used to identify the optimal cutoff of serum Cys-c levels for predicting DPN in patients with T2DM.
 RESULTS: Serum Cys-c levels were significantly higher in the DPN group than that in the NDPN group [(1.04±0.43) vs (0.80±0.25) mg/L, P<0.01]. Correlation analysis showed that serum Cys-c levels were positively correlated with age, body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), ACR, VPT, pulse pressure (PP), white blood cell( WBC) , red cell distribution width (RDW), hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) (r=0.410, 0.115, 0.613, 0.433, 0.291, 0.300, 0.156, 0.129, 0.282, 0.314, 0.236, respectively, P<0.05 or P<0.01); and negatively correlated with diastolic blood pressure (DBP), eGFR and indirect bilirubin (IBIL) (r=-0.135, -0.647, -0.114, respectively, P<0.05 or P<0.01). Serum Cys-c levels in T2DM patients were positively correlated with VPT after adjusting for gender, age, BMI, ACR and eGFR (r=0.235, P<0.01). Multiple regression analysis revealed that VPT, age, SCr, eGFR, PP, ACR and HbA1C were independent related factors affecting serum Cys-c levels in T2DM patients. Compared with those in the low Cys-c levels group, the prevalence rate and VPT value was increased in the high Cys-c levels group (all P<0.01). Binary logistic regression analysis found that age, Cys-c and HbA1C were independent risk factors for predicting DPN in T2DM patients (all P<0.01). ROC curve analysis revealed that the optimal cutoff of Cys-c to predict DPN in T2DM patients was 0.996 mg/L, the sensitivity was 43.9%, the specificity was 83.7%, and the area under curve was 0.663.
 CONCLUSION Serum Cys-c levels are well correlated with VPT in patients with T2DM. When the serum Cys-c levels>0.996 mg/L, the predicts have high risk of DPN in T2DM patients, which might be related to diabetic nephropathy, oxidative stress and inflammatory reaction induced by advanced age, hyperglycemia and hypertension.
Cystatin C ; blood ; Diabetes Mellitus, Type 2 ; blood ; Diabetic Neuropathies ; blood ; Humans ; Incidence ; Perception ; physiology ; Prevalence ; Risk Factors ; Vibration