[Show abstract][Hide abstract] ABSTRACT: Aims
A20 is a negative regulator of nuclear factor kappa B activation and the central gatekeeper in inflammation and immunity. While its role in type 1 diabetes has been widely studied, its expression level in immune cells from type 2 diabetes (T2D) and latent autoimmune diabetes in adult (LADA) patients remains unclear. This study aimed to clarify whether the expression of A20 is altered in patients with T2D or LADA.
Quantitative real-time polymerase chain reaction and western blotting were utilized to determine the expression of A20 mRNA and protein respectively in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n = 36) or LADA (n = 17) and sex- and age-matched healthy controls (n = 34).
The mRNA and protein expression of A20 in PBMCs from T2D and LADA patients was significantly decreased compared with healthy controls (P < 0.05). Furthermore, A20 mRNA and protein expression was significantly lower in newly diagnosed T2D patients (≤1 year since diagnosis) than in patients with a long T2D duration (>1 year since diagnosis) (P < 0.05).
Our results suggest that decreased expression of A20 in PBMCs may be involved in the pathogenesis of diabetes, and targeting A20 may offer a potential therapeutic tool in the treatment of diabetes.
Diabetes Research and Clinical Practice 10/2014; 106(3). DOI:10.1016/j.diabres.2014.09.014 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims
The assessment of transcutaneous oxygen pressure (TcPO2) may serve as a non-invasive and lower-cost alternative to nerve conduction studies (NCSs) for the diagnosis of diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether the measurement of TcPO2 is useful for evaluating DPN.
We performed a cross-sectional study of 381 consecutive hospitalized diabetic patients classified by clinical examination and NCS as having DPN. Anthropometric and metabolic parameters were assessed. The TcPO2 examination was performed in both supine and sitting positions.
Three hundred and one patients had DPN. The TcPO2 in both the supine and sitting positions was highest in the Non-DPN group and lower in the confirmed DPN group than the other three groups (p < 0.001). The Non-DPN group had the lowest sitting-supine position difference in TcPO2 among the groups (p < 0.001). The risk factors strongly associated with DPN included sitting-supine position difference in TcPO2 (OR =4.971, p < 0.001), diabetic retinopathy (DR) (odds ratio [OR] =3.794, p =0.002), and HbA1c (OR =1.534, p =0.033). The area under the curve (AUC) of the sitting-supine position difference in TcPO2 was 0.722 and revealed an optimal cutoff point for the identification of DPN (19.5 mmHg) that had a sensitivity of 0.611 and a specificity of 0.738 based on AUC analysis.
This large study of diabetic patients confirms that the sitting-supine position difference in TcPO2 is higher in DPN patients than control subjects, indicating that TcPO2 examination is a promising valuable diagnostic tool for DPN.
Diabetes Research and Clinical Practice 09/2014; 105(3). DOI:10.1016/j.diabres.2014.05.012 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Insulin resistance (IR) is closely correlated with cardiovascular disease (CVD). Retinol-binding protein 4 (RBP4) is a novel adipokine that modulates the action of insulin in various diseases. This study addressed the relationship between RBP4 and IR in newly diagnosed essential hypertension.
Serum RBP4, anthropometric and metabolic parameters were determined in 267 newly diagnosed essential hypertensive patients not taking antihypertensive medications. The patients along with 64 control (NC) normotensive and lean subjects paired by age and sex were divided into two groups depending on body mass index (BMI), hypertension with obesity (HPO) and hypertension without obesity (HP).
A striking difference was observed in RBP4 levels between the HP and NC groups. Significantly higher levels were noted in the HP group compared with the NC group; slightly, but not significantly, lower levels were observed in the HPO group compared with the HP group. After adjusting for BMI, WC and WHR, a modestly linear relationship was observed between RBP4 levels and SBP (r = 0.377; p = 0.00), DBP (r = 0.288; p = 0.00) and HOMA-β(r = 0.121; p = 0.028). Multiple stepwise regression analysis showed that SBP, WHR and drinking were independently related with serum RBP4 levels.
The results of this study indicated that RBP4 levels were increased in naive hypertensive patients; however, no differences were observed in obese or non-obese hypertensive subjects. Our data suggest for the first time that RBP4 levels are significantly increased but do not contribute to the development of IR in newly diagnosed hypertensive Chinese patients.
[Show abstract][Hide abstract] ABSTRACT: Background and AimThe red blood cells count is closely associated with insulin resistance (IR), which is origin of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the correlation of red blood cells (RBC) indices with NAFLD.MethodsA total of 977 cases including 446 NAFLD patients and 531 controls were enrolled and examined for biochemical and metabolic indices. RBC, hematocrit (HCT), Hemoglobin (HGB), insulin and ferritin were detected. The IR indicator HOMA2-IR and fatty liver index (FLI) were calculated. The correlation analysis was assessed by spearman rank test. Receiver operating characteristic was used to evaluate diagnostic performance. After quartile classification of RBC indices, logistic regression analysis was conducted to evaluate the odds ratios (OR) of NAFLD .ResultsRBC, HCT and HGB levels were obviously higher in NAFLD group. RBC, HCT and HGB showed significant positive correlation with HOMA2-IR and NAFLD. Multivariate analysis revealed HGB, ferritin and triglyceride as independent parameters associated with NAFLD. The predictive value after combination of HGB with ferritin and triglyceride was equal to FLI. After adjustment for age, BMI, systolic BP, TC, TG, LDL-C, HDL-C and smoking, comparing the groups with the highest and lowest HGB, HCT and RBC, the OR (95% confidence intervals) of NAFLD were 2.369(1.279-4.368) (P<0.05), 1.504(0.819-2.713) (P>0.05), and 2.332(0.823-2.550) (P>0.05) in male. In female, the OR were 2.541(1.118-5.771), 3.578(1.464-8.748) and 3.215(1.387-7.455) (P<0.05).Conclusions
Our data suggest that HGB combined with triglyceride and ferritin may serve as the indicator of predicting NAFLD.
Journal of Gastroenterology and Hepatology 03/2014; 29(7). DOI:10.1111/jgh.12580 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Numerous evidences demonstrated that type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8(+) T cells play an important role in the development of T1D. Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D. However, ZnT8-associated CTL specific-peptides have not been identified. In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice. The results demonstrated that peptides of ZnT8 containing residues 107-115, 115-123 and 145-153 could elicit specific CTLs in vitro, and induce diabetes in mice. The results suggest that these specific peptides are novel HLA-A*0201-restricted CTL epitopes, and could have therapeutic potential in preventing of T1D disease.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to examine the patterns of Sfrp5 mRNA expression and protein secretion during the dynamic process of adipocyte differentiation, and investigate the potential role of Sfrp5 in insulin resistance in adipocytes. 3T3-L1 pre-adipocytes were induced for differentiation and RT-PCR and ELISA assays were performed to determine Sfrp5 mRNA expression and protein secretion. The results showed that with the differentiation and maturity of pre-adipocytes, transcription and protein secretion of Sfrp5 gradually increased and peaked on the 9th day of differentiation. Sfrp5 mRNA expression in mature adipocytes was decreased by 20%, 22% and 32% upon treatment with dexamethasone, insulin, and TNF, respectively, while Sfrp5 protein secretion was decreased by 15%, 17% and 30%, correspondingly. In contrast, Sfrp5 mRNA expression in mature adipose was increased by 34% and 19% upon treatment with rosiglitazone and metformin, respectively, while Sfrp5 protein secretion was increased by 10% and 6%, correspondingly. In conclusion, Sfrp5 mRNA expression and protein secretion depend on the differentiation of adipocytes. The dysregulation of Sfrp5 expression and secretion is directly correlated with insulin resistance. Upregulation of Sfrp5 expression and secretion in adipocytes appears to be one crucial mechanism by which rosiglitazone and metformin improve insulin sensitivity.
Cell Biology International 05/2012; 36(9). DOI:10.1042/CBI20120054 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine whether the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator linking angiogenesis and metabolism, could enhance the engraftment and angiogenesis of mesenchymal stem cells (MSCs) in diabetic hindlimb ischemia, we engineered the overexpression of PGC-1α within MSCs using an adenoviral vector encoding green fluorescent protein and PGC-1α, and then tested the survivability and angiogenesis of MSCs in vitro and in vivo. Under the condition of hypoxia concomitant with serum deprivation, the overexpression of PGC-1α in MSCs resulted in a higher expression level of hypoxia-inducible factor-1α (Hif-1α), a greater ratio of B-cell lymphoma leukemia-2 (Bcl-2)/Bcl-2-associated X protein (Bax), and a lower level of caspase 3 compared with the controls, followed by an increased survival rate and an elevated expression level of several proangiogenic factors. In vivo, the MSCs modified with PGC-1α could significantly increase the blood perfusion and capillary density of ischemic hindlimb of the diabetic rats, which was correlated to an improved survivability of MSCs and an increased level of several proangiogenic factors secreted by MSCs. We identified for the first time that PGC-1α could enhance the engraftment and angiogenesis of MSCs in diabetic hindlimb ischemia.
[Show abstract][Hide abstract] ABSTRACT: To identify better cells for the treatment of diabetic critical limb ischemia (CLI) and foot ulcer in a pilot trial.
Under ordinary treatment, the limbs of 41 type 2 diabetic patients with bilateral CLI and foot ulcer were injected intramuscularly with bone marrow mesenchymal stem cells (BMMSCs), bone marrow-derived mononuclear cells (BMMNCs), or normal saline (NS).
The ulcer healing rate of the BMMSC group was significantly higher than that of BMMNCs at 6 weeks after injection (P=0.022), and reached 100% 4 weeks earlier than BMMNC group. After 24 weeks of follow-up, the improvements in limb perfusion induced by the BMMSCs transplantation were more significant than those by BMMNCs in terms of painless walking time (P=0.040), ankle-brachial index (ABI) (P=0.017), transcutaneous oxygen pressure (TcO(2)) (P=0.001), and magnetic resonance angiography (MRA) analysis (P=0.018). There was no significant difference between the groups in terms of pain relief and amputation and there was no serious adverse events related to both cell injections.
BMMSCs therapy may be better tolerated and more effective than BMMNCs for increasing lower limb perfusion and promoting foot ulcer healing in diabetic patients with CLI.
Diabetes research and clinical practice 04/2011; 92(1):26-36. DOI:10.1016/j.diabres.2010.12.010 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was to explore the relationship of serum BMP7 with insulin secretion and metabolic parameters in non-diabetic individuals. Serum BMP7 concentrations positively correlated with HOMA2-%B (insulin secretion index) and fasting insulin. Our findings suggested that BMP7 may stimulate insulin secretion and improve islet cell function in humans.
Diabetes research and clinical practice 03/2011; 93(1):e21-4. DOI:10.1016/j.diabres.2011.03.010 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent human genetic studies have revealed that common variants of the zinc transporter 8 (ZnT-8) gene are strongly associated with type 2 diabetes mellitus (T2DM). ZnT-8 has been suggested as a potential candidate in the regulation of insulin secretion in pancreatic β-cells. In this study, we aimed to explore the expression of ZnT-8 in the development of T2DM. The expression of ZnT-8 was investigated in the pancreas and adipose tissue of homozygous db/db mice compared to heterozygous sibling db/+ mice (n=6-8). Furthermore, the effect of Exendin-4 (an analogue of glucagon-like peptide-1) on ZnT-8 expression was examined in the db/db mice. Exendin-4 or vehicle (control) was administered (i.p., 1 nmol/kg) to diabetic 8-week-old db/db mice daily for 14 days (n=8). The results revealed that ZnT-8 protein levels in the pancreas of db/db mice were reduced, accompanied by a decrease in ZnT-8 mRNA. ZnT-8 mRNA and protein levels were also significantly reduced in the epididymal and visceral fat of the db/db mice. Treatment with Exendin-4 up-regulated ZnT-8 gene expression in the pancreas of the db/db mice, but did not affect its expression in adipose tissue. These findings suggest that ZnT-8 synthesis in the pancreas and adipose tissue is down-regulated in db/db mice. Reduced ZnT-8 production in the pancreas may advance defects in insulin secretion in diabetes. These may be reversed, at least partially, by the administration of Exendin-4.
Molecular Medicine Reports 01/2011; 4(1):47-52. DOI:10.3892/mmr.2010.392 · 1.55 Impact Factor