Liu F.,Central South University |
Chen D.-D.,Shanghai Institute of Diabetes |
Sun X.,Shanghai University |
Xie H.-H.,Shanghai Institute of Diabetes |
And 3 more authors.
Diabetes | Year: 2014
Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydroxythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with DL-propargylglycine (PAG) or saline for 18 days. Plasma H 2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice. © 2014 by the American Diabetes Association.
Hu Y.,Shanghai JiaoTong University |
Hu Y.,Shanghai Institute of Diabetes |
Liu F.,Shanghai JiaoTong University |
Liu F.,Shanghai Institute of Diabetes |
And 9 more authors.
European Journal of Endocrinology | Year: 2014
Objective: Serum cystatin C (CysC) is a sensitive marker of kidney function and recent studies have shown that CysC plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study was to explore the relationship between serum CysC and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. Methods: In total, 937 type 2 diabetic patients were enrolled in this cross-sectional study. Serum CysC concentration was measured by immunoturbidimetry. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer, and electromyogram. Results: Serum CysC levels were significantly higher in DPN patients (1.3 (1.1-1.5) mg/l) compared with patients with signs of DPN (1.1 (0.9-1.3) mg/l, P<0.001) and non-DPN patients (1.0 (0.9-1.3) mg/l, P< 0.001). Multiple regression analysis revealed that DPN was associated with age, diabetes duration, HbA1c, and serum CysC. Spearman's correlation analysis showed that serum CysC was closely related with age, sex, diabetes duration, hypertension, glomerular infiltration rate, and serum creatinine (Cr) level. The patients were divided into quartiles according to the serum CysC levels. Compared with quartile 1 (referent), the risk of DPN was significantly higher in quartile 2 (odds ratio (OR), 1.753; 95% CI, 1.055-2.912; P<0.05), quartile 3 (OR, 2.463; 95% CI, 1.445-4.917; P<0.01), and quartile 4 (OR, 5.867; 95% CI, 2.075-16.589; P<0.01). Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum CysC to indicate DPN was 1.25 mg/l in male patients and 1.05 mg/l in female patients. High serum CysC level indicated a onefold higher risk of DPN. Conclusions: High serum CysC level is closely associated with DPN and may be a potential biomarker for DPN in type 2 diabetic patients. © 2014 European Society of Endocrinology
Liu X.-H.,Shanghai Institute of Diabetes |
Wei L.,Shanghai Institute of Diabetes |
Wang L.-Y.,Shanghai Institute of Diabetes |
Zhu C.-Y.,Shanghai Institute of Diabetes |
And 2 more authors.
National Medical Journal of China | Year: 2010
Objective: To study the RBP4 mRNA expression between subcutaneous and visceral adipose tissue in obese and type 2 diabetic patients and to investigate the factors that influence RBP4 mRNA expression in Human visceral adipose tissue. Methods: 9 individuals with normal weight normal glucose regulation subjects, 9 obesity subjects and 9 type 2 diabetes subjects were enrolled. All of the subjects were prepared to undergone an operation because of nondiabetes disease. Subcutaneous and visceral adipose tissue were taken out as soon as cultured. RT-PCR and Real-time PCR were used to assay the relative expression of RBP4 mRNA. Results: RBP4 mRNA level in visceral adipose tissue of obesity group was (2.10±1.84), and that of type 2 diabetes group was (1.54±0.46), both were significantly higher than that in normal weight normal glucose group (0.75±0.28, P<0.01, P<0.05). RBP4 mRNA level in subcutaneous adipose tissue of the three groups were (1.05±0.15 vs 0.99±0.14 vs 1.13±0.07), no difference among them (P>0.05). Insulin, dexamethasone, pioglitazone, free fatty acids can significantly increase RBP4 mRNA expression, compared with the control group, respectively, have an increase of 2.13 times, 0.84 times, 2.04 times, 4.88 times; however, tumor necrosis factor-α can significantly lower RBP4 mRNA level, compared with the control group decreased by 38%. Conclusion: RBP4 mRNA expression in visceral adipose tissue were significantly higher in obesity and type 2 diabetes subjects. In vitro system, RBP4 gene expression in visceral adipose tissue of normal weight normal glucose subjects was regulated by insulin, dexamethasone, pioglitazone, palmitic acid and TNF-α, such factors were also participated in the pathophysiological process of insulin resistance and type 2 diabetes.
PubMed | Shanghai Institute of Diabetes
Type: Journal Article | Journal: Zhonghua yi xue za zhi | Year: 2013
To observe the effects of leptin on activity of GSK-3 and explore its mechanism.C2C12 myoblasts differentiated for 3 days into myotubes in differentiation medium. Myotubes were stimulated by leptin (100 nmol/L) for 0, 5, 15 or 30 min respectively. Western blot was used to detect the expression levels of GSK-3 and phospho-GSK-3 (ser-9). Co-immunoprecipitation (CO-IP) was performed to determine the relationship among APPL1, leptin receptor and GSK-3 in the presence or absence of leptin. The expression level of GSK-3 at phospho-GSK-3 (ser-9) was detected in APPL1-suppressed C2C12 myotube while that of APPL1 at phospho-APPL1 (ser-401) determined in GSK-3 overexpressed/inhibited C2C12 cell.Leptin time-dependently increased the phosphorylation level of GSK-3 at ser-9 in C2C12 cell, and the pGSK-3 level in cells incubated by leptin for 30 min was as 4.08 times as which in control cells (P < 0.01). The triple complex of APPL1, leptin receptor and GSK-3, in the presence of leptin, the binding capacity between APPL1 and GSK-3 was stronger. The level of phospho-GSK-3 was significantly lower in APPL1-suppressed C2C12 cell compared with that in control cells. And the phosphorylation of APPL1 at ser-401 could be induced by GSK-3.Leptin promotes muscle glycogen synthesis by inducing phosphorylation of GSK-3 in C2C12 cell. Such a function may be mediated by the triple complex of APPL1, leptin receptor and GSK-3. Meanwhile, GSK-3 can also increase the phosphorylation of APPL1 at ser-401.