Dongfang Liu

Chongqing Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (6)25.16 Total impact

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    ABSTRACT: OBJECTIVE: Women with polycystic ovary syndrome (PCOS) mostly have profound insulin resistance (IR) and β-cell dysfunction. Although thioredoxin-interacting protein (TXNIP) is a major regulator in IR and insulin secretion, no data on the plasma TXNIP level in patients with PCOS are available. This study aimed to determine the plasma TXNIP level and discuss the relationship between TXNIP and β-cell dysfunction/IR in PCOS patients. PATIENTS: Eighty-three women with PCOS and 52 controls. MEASUREMENTS: Insulin sensitivity was expressed by M value obtained from euglycaemic-hyperinsulinaemic clamp. Homeostatic model assessment for β-cell function (HOMA-β), △Ins30 /△Glu30 , and AUCins/glu were considered as the indices of fasting state, early-phase, and total insulin secretion during oral glucose tolerance test, respectively. To evaluate β-cell function adjusted for insulin sensitivity, disposition index (DI) was used: basal DI (DI0 ), early-phase DI (DI30 ), and total DI (DI120 ). Plasma TXNIP levels were measured by enzyme-linked immunosorbent assay. DESIGN: Case-control study. RESULTS: PCOS patients had higher serum TXNIP, whereas lower M value, DI0 , DI30 , and DI120 than controls (P < 0.05); their TXNIP correlated positively with weight, waist-to-hip ratio (WHR), body mass index (BMI), Ins0 , Ins120 , and HOMA-β and correlated negatively with M value and DI120 (P < 0.05). Multiple stepwise regression analysis indicated that TXNIP remained associated with M value in PCOS subjects, after adjusting weight, BMI, WHR, HOMA-β, Ins0 , Ins120 , and DI120 . However, no relationship between TXNIP and impaired β-cell function was found. CONCLUSION: Serum TXNIP is elevated in women with PCOS and may be a contributing factor for IR. © 2013 Blackwell Publishing Ltd.
    Clinical Endocrinology 03/2013; · 3.40 Impact Factor
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    ABSTRACT: OBJECTIVE Zinc-α(2)-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies.RESEARCH DESIGN AND METHODS Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial.RESULTSCirculating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA(1c), and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels.CONCLUSIONS We conclude that ZAG may be an adipokine associated with insulin resistance.
    Diabetes care 12/2012; · 7.74 Impact Factor
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    ABSTRACT: Background Thioredoxin-interacting protein (Txnip), an inhibitor of thioredoxin (Trx), increases in diabetic nephropathy and promotes oxidative stress. The Ang II receptor blocker telmisartan may protect renal function in diabetic models and patients via multiple effects including antioxidation. However, its mechanism has not been fully elucidated, and its relationship to Txnip remains unclear. Aim This study aimed to investigate whether telmisartan ameliorates oxidative stress by regulating Txnip and Trx expression in type 2 diabetic rat kidneys and explore the possible relationship between renoprotection by telmisartan and Txnip. Methods Twenty-one rats were equally divided into control (C), streptozotocin-induced diabetic (D), and telmisartan-treated diabetic (T) groups. Txnip and Trx expression in rat kidneys was analysed by immunohistochemistry, RT-PCR, and western blot. Peroxisome proliferator-activated receptor-γ (PPARγ), NADPH oxidase activity, and parameters of renal function and oxidative stress were also measured. Results Trx and PPARγ were significantly decreased, and Txnip expression and NADPH oxidase activity markedly increased, in the D and T groups compared to the C group. After telmisartan treatment, Trx and PPARγ were upregulated, while Txnip expression and NADPH oxidase activity were downregulated. Parameters of renal function and oxidative stress were improved by telmisartan. Conclusion Telmisartan ameliorates oxidative stress and protects renal function in type 2 diabetic rat kidneys. The downregulation of Txnip by telmisartan may be associated with PPARγ activation.
    Journal of endocrinological investigation 11/2012; · 1.65 Impact Factor
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    ABSTRACT: Context:Secreted frizzled-related protein-5 (Sfrp5) is a novel adipocyte-secreted hormone that has been shown to link obesity with diabetes. Studies in mice have revealed that Sfrp5 represents a potential target for the control of obesity-linked abnormalities in glucose homeostasis.Objective:Our objective was to gain insight into the physiological role of circulating Sfrp5 in humans.Patients and Design:We conducted a series of cross-sectional and interventional studies of the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Subjects included 104 healthy subjects, 101 with impaired glucose tolerance, and 112 with newly diagnosed type 2 diabetes mellitus and, in a separate study, 30 healthy women, and 32 women with polycystic ovarian syndrome (PCOS). Oral glucose tolerance test and euglycemic-hyperinsulinemic clamp were performed to assess glucose tolerance and insulin sensitivity.Results:Circulating Sfrp5 was significantly lower in both impaired glucose intolerance and newly diagnosed type 2 diabetes mellitus than in individuals with normal glucose tolerance (P < 0.01). Overweight/obese subjects had significantly lower Sfrp5 levels than lean individuals (P < 0.01), but females had higher Sfrp5 levels than males (P < 0.05). In a separate study, Sfrp5 levels were lower in PCOS women than healthy women (P < 0.05). Moreover, circulating Sfrp5 correlated with markers of adiposity, including body mass index, waist-to-hip ratio, percent body fat, homeostasis model assessment of insulin resistance, lipid profile, and adiponectin. Hyperglycemia decreased circulating Sfrp5 levels, whereas liraglutide increased Sfrp5 levels. In the euglycemic-hyperinsulinemic state, circulating Sfrp5 was significantly decreased in healthy women but not in PCOS women.Conclusions:We conclude that circulating Sfrp5 is likely to play a major role in insulin resistance in humans.
    The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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    ABSTRACT: To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma vaspin levels in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty patients with severe newly diagnosed T2DM, 37 subjects with impaired glucose tolerance (IGT) and 38 gender-, age- and body mass index (BMI)-matched normal GT (NGT) controls participated in the study. The T2DM group was treated with CSII for 2 weeks. Euglycemic-hyperinsulinemic clamps were performed in 16 subjects of the T2DM group. Plasma vaspin concentrations were measured with a commercial ELISA kit. The relationship between plasma vaspin levels and metabolic parameters was also analyzed. Fasting plasma vaspin levels were higher in the T2DM group than in IGT and NGT groups (1.83±0.55 vs 0.51±0.21 vs 0.53±0.24 μg/l, P<0.05), but there was no difference between IGT and NGT groups. In T2DM patients, fasting plasma vaspin concentrations were significantly decreased after CSII treatment for 2 weeks (1.83±0.55 vs 1.19±0.57 μg/l, P<0.05), accompanied by significant amelioration of insulin sensitivity and glucose control. The changes in plasma vaspin levels were positively associated with the amelioration of insulin resistance (IR) shown by the changes in homeostasis model assessment of IR. Plasma vaspin level is associated with IR and is significantly reduced following short-term CSII treatment.
    European Journal of Endocrinology 04/2011; 164(6):905-10. · 3.14 Impact Factor
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    ABSTRACT: Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue, which increases insulin sensitivity in human adipocytes. However, its pathophysiologic role in humans remains largely unknown. The objective of this study is to assess plasma omentin-1 levels in patients with type 2 diabetes mellitus (T2DM) and matched control subjects and to investigate the effects of liraglutide on plasma omentin-1 levels in patients with T2DM. Thirty T2DM patients with poor glycemic control after more than 3 months of treatment with one or two OHA(s) (T2DM), and 30 matched normal glycaemic controls (NGT) participated in the study. The T2DM group was given an injection of liraglutide once-daily for 16 weeks. Plasma omentin-1 levels were measured by enzyme-linked immunosorbent assay and the relationship between plasma omentin-1 levels and metabolic parameters was also analyzed. Plasma omentin-1 levels were lower in T2DM than in the control (19.3 ± 4.0 μg/L vs. 26.4 ± 6.0 μg/L, P < 0.01). Plasma omentin-1 levels increased significantly in T2DM patients after treatment with liraglutide compared with pre-treatment (19.3 ± 4.0 μg/L vs. 21.2 ± 3. 9 μg/L, P < 0.01). In all diabetic patients, multiple regression analysis showed that FINS and HOMA-IR were independently associated with plasma omentin-1 levels. In T2DM patients, plasma omentin-1 levels decreased, but significantly increased after the treatment with liraglutide and metformin. These data suggest that liraglutide may play a role in increasing omentin-1 levels in T2DM patients.
    Diabetes research and clinical practice 03/2011; 92(3):368-74. · 2.74 Impact Factor