Yeping Yang

Adipophilin affects the expression of TNF-α, MCP-1, and IL-6 in THP-1 macrophages

Macrophages accumulated in the arterial intima play an important role in the development of atherosclerosis by producing a large number of proinflammatory cytokines which accelerate the disease. Recent studies show that adipophilin might be involved in inflammatory processes in macrophages. In this study, we observe the effect of adipophilin on proinflammatory cytokine expression and secretion in THP-1 macrophages. SiRNA and adipophilin gene overexpression mediated by an pEGFP-C3 vector were used to observe the effect of adipophilin on proinflammatory cytokines in THP-1 macrophages in vitro. Realtime PCR and enzyme-linked immunosorbent assay (ELISA) were applied to detect the production of tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). It was found that acetylated low-density lipoprotein (AcLDL), pioglitazone [a peroxisome proliferator-activated receptor γ (PPARγ) agonist] increased adipophilin expression in macrophages, while glucose had no such affect. It was also shown that adipophilin augments TNF-α, MCP-1, and IL-6 expression in AcLDL induced macrophages. Our results suggest that adipophilin augment inflammation in macrophages, which might be one role of adipophilin in atherosclerosis.

Early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus and impaired glucose tolerance

AIM The aim of this study was to investigate early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT). METHODS The study subjects underwent an oral glucose tolerance test (OGTT) and were then divided into three groups, according to plasma glucose level: those in the normal glucose tolerance (NGT) group had fasting plasma glucose (FPG)<6.1mmol/L and 2h postload glucose (2hPPG)<7.8mmol/L; those in the IGT group had FPG<6.1mmol/L and 2hPPG>or=7.8mmol/L; and those in the T2DM group had FPG>or=7.0mmol/L or 2hPPG>or=11.1mmol/L. Haemodynamic variables and brachial-ankle pulse-wave velocities (baPWV) in the three groups were compared. RESULTS The baPWV value increased with increases in plasma glucose, and was significantly and positively correlated to age, FPG, 2hPPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference and waist-to-hip ratio. Significant differences were found between the baPWV values in the NGT and IGT groups (1602+/-347 vs 1707+/-351cm/s, respectively; P=0.005), and between the NGT and DM groups (1602+/-347 vs 1762+/-381, respectively; P<0.001). The results of multiple regression analyses showed that 2hPPG was closely related to baPWV as well as to SBP and DBP. CONCLUSION Early-stage atherosclerosis is present in newly diagnosed, untreated T2DM and IGT patients, and it may be that its early assessment, along with good control of hypertension and hyperglycaemia, will help to delay its progression.

Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy

Aims  Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, the multifactorial nature of DN supports the application of combined markers as a diagnostic tool. Thus, another screening approach, such as protein profiling, is required for accurate diagnosis. Surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS) is a novel method for biomarker discovery. We aimed to use SELDI and bioinformatics to define and validate a DN‐specific protein pattern in serum.

Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

Aims  Our aim was to assess performances of the Cockcroft–Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks.

Serum high-density lipoprotein cholesterol and progression to arterial stiffness in middle-aged and elderly Chinese

BACKGROUND AND AIMS Low high-density lipoprotein cholesterol (HDL-c) is a risk factor for cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is an indicator of arterial stiffness, which is recognized as a predictor of cardiovascular disease. The aim of this study was to investigate the association between HDL-c and baPWV among middle-aged and elderly Chinese. METHODS A total number of 1133 Chinese (430 men, 703 women) aged from 50 to 90 years old were recruited from Shanghai downtown district. The baPWV and major cardiovascular risk factors of the participants were measured. RESULTS Serum HDL-c was negatively correlated with baPWV (r = -0.143, P < 0.001) after adjustment for age and gender. Multivariate linear regression analysis demonstrated that age (P < 0.001), systolic blood pressure (P < 0.001), HDL-c (P < 0.001), smoking (P = 0.001), BMI (P = 0.002), fasting plasma glucose (P = 0.004), and white blood cell (P = 0.005) were independently associated with baPWV. After multiple adjustments, participants in the highest quartile of HDL-c had an odds ratio of 0.442 (95% CI 0.268-0.729) for developing high arterial stiffness compared with participants in the lowest quartile. The association remained significant after further adjustment for major cardiovascular risk factors. CONCLUSION HDL-c has an independent protective effect on arterial stiffness in middle-aged and elderly Chinese. Early detection of HDL-c level is important in high risk populations with arterial stiffness. Increasing HDL-c level may be an attractive therapeutic target for the prevention of arterial function and subsequent disease.

An Evaluation of the Diabetic Kidney Disease Definition in Chinese Patients Diagnosed with Type 2 Diabetes Mellitus

The concomitant presence of retinopathy may be helpful in discriminating kidney pathology in type 2 diabetes. This cross-sectional study evaluated the ability to predict the likelihood of patients having diabetic kidney disease (DKD) by comparing the percentage incidence of diabetic retinopathy in different subgroups of Chinese patients with type 2 diabetes (n = 668). The prevalence of chronic kidney disease in the patients was 63.3% (6.6% with DKD, 41.0% with possible DKD and 15.7% with non-diabetic renal disease [NDRD]). The percentage of patients with diabetic retinopathy in the DKD group (63.6%) was significantly higher than in the possible DKD group (24.9%) and the NDRD group (19.0%). DKD was independently associated with diabetic retinopathy based on logistic regression analysis. The likelihood of DKD occurrence as defined by the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative™ of the USA is applicable to Chinese patients with diabetes. Diabetic retinopathy was more prevalent in patients with DKD compared with patients with possible DKD or NDRD.

The New Unified International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute Metabolic Syndrome definition: does it correlate better with C-reactive protein in Chinese patients diagnosed with type 2 diabetes?

This study evaluated the association between high-sensitivity C-reactive protein (hsCRP) and metabolic syndrome, defined by the definition proposed by the International Diabetes Federation (IDF), American Heart Association (AHA) and National Heart, Lung, and Blood Institute (NHLBI) versus the older IDF definition, in 506 Chinese patients with type 2 diabetes. Anthropometric and biochemical parameters were compared and analysed using multivariate linear regression models. Serum hsCRP was higher in patients with metabolic syndrome compared with those without metabolic syndrome for both definitions and increased as the number of components of metabolic syndrome increased (after adjusting for age, gender and smoking). Patients with metabolic syndrome according to the IDF/AHA/NHLBI but not the IDF definition had significantly higher hsCRP levels than those not meeting either definition and similar hsCRP levels to those meeting both definitions. Serum hsCRP levels were significantly associated with metabolic syndrome according to the IDF definition after adjusting for age, gender and smoking. Adding metabolic syndrome status according to the IDF/AHA/NHLBI definition significantly increased the fit of the multivariate linear regression model. The new IDF/AHA/NHLBI definition of metabolic syndrome may have a stronger relationship with serum hsCRP than the IDF definition.

The Association of Dysglycaemia and Cardiovascular Disease in Patients with Metabolic Syndrome

The objective of this study was to investigate the relationship between increased prevalence of cardiovascular disease and glucose regulation status in Chinese patients with metabolic syndrome (MetS). All patients underwent an oral glucose tolerance test (2-h post-load plasma glucose) to determine their glucose regulation status and had their brachial–ankle pulse wave velocity (baPWV) measured. Of the 590 patients included in the study, 115 (19.5%) had normal glucose tolerance, 114 (19.3%) had impaired fasting glucose (IFG) alone, 38 (6.4%) had impaired glucose tolerance (IGT) alone, 197 (33.4%) had diabetes mellitus and 126 (21.4%) had combined glucose intolerance (CGI; IFG plus IGT). Patients with diabetes mellitus had a significantly higher baPWV compared with all other groups and patients with CGI had a significantly higher baPWW compared with patients with IFG. Dysglycaemia was common in patients with MetS. An increased prevalence of cardiovascular disease in patients with MetS was related to their glucose regulation status.

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, n = 63) or a direct-surgery group (DS, n = 30), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

High glucose-induced ubiquitylation of G6PD leads to the injury of podocyte

Oxidative stress contributes substantially to podocyte injury in diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase is critical in maintaining NADPH, an important cofactor for antioxidant system. Here, we hypothesized that high glucose induces ubiquitylation and degradation of G6PD, which injures podocytes by reactive oxygen species (ROS) accumulation. We found that both G6PD protein expression and G6PD activity was decreased in kidneys of both diabetic patients and diabetic rodents. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD induced podocyte apoptosis. In G6PD deficient mice, podocyte apoptosis was also largely increased. High glucose had no effect on G6PD mRNA level but it caused decreased G6PD protein expression, which was mediated by the ubiquitin proteasome pathway. Furthermore, von Hippel−Lindau (VHL), an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on lysine residues 366/403. Our data suggest that high glucose induces ubiquitylation of G6PD by VHL, which leads to ROS accumulation and podocyte injury.