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腹腔脂肪型丝氨酸蛋白酶抑制剂

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维斯盼（Vaspin, visceral adipose tissue-derived serpin)

北京爱迪博生物2009年自主开发Vaspin酶联试剂盒， 出口国际市场

维斯盼（Vaspin, visceral adipose tissue-derived serpin)是 日本学者Hidad于2005年首次报告一种腹腔脂肪组织合成和分泌的丝氨酸蛋白酶抑制剂。人的维斯盼有395个氨基酸残基，大鼠和小鼠的维斯盼分别有 392和394个氨基酸残基。维斯盼属于丝氨酸蛋白酶抑制剂家族。北京爱迪博生物科技对维斯盼进行一系列研究开发，并命名为腹腔脂肪型丝氨酸蛋白酶抑制 剂。2009年爱迪博生物开发成功酶联试剂盒可以检测人和大鼠的样本， 并开始出口到国际市场。日本学者的研究结果发现，大鼠腹腔脂肪型丝氨酸蛋白酶抑制剂的基因表达或血清水平在糖尿病的发病过程中呈现明显降低趋势。应用胰岛素或胰岛素的增敏剂 治疗，糖尿病大鼠模型，可以使大鼠腹腔脂肪型丝氨酸蛋白酶抑制剂的基因表达或血清水平恢复到正常对照水平。给肥胖小鼠喂养高糖饲料的同时腹腔注射维斯盼， 显著改善糖耐量和胰岛素的敏感度、恢复肥胖小鼠的血糖水平。此外，维斯盼还可以逆转肥胖小鼠体内与胰岛素抵抗相关基因的表达， 如瘦素、抵抗素、肿瘤坏死因子-阿尔法和糖转运载体-4等。基因芯片检测显示，维斯盼治疗肥胖小鼠使50%的高脂肪或高糖饮食所诱导的基因表达发生逆转。 提示，维斯盼作为腹腔脂肪型丝氨酸蛋白酶抑制剂，不仅是一种潜在的糖尿病检测的生物表示物，还具有强大的胰岛素增敏作用和治疗代谢综合征的作用。

丝 氨酸蛋白酶抑制剂是二型糖尿病大鼠腹腔脂肪组织分泌的一个胰岛素增敏性脂肪因子。我们的研究结果显示丝氨酸蛋白酶抑制剂在脂肪组织的表达和肥胖和糖代谢有 关。但是肥胖和二型糖尿病患者血清中丝氨酸蛋白酶抑制剂的含量以及调节变化还不清楚。我们建立了一中酶联免疫定量分析试剂盒分别检测了187例试验观察对 象伴有肥胖、脂肪堆积、胰岛素敏感性和糖耐量异常的血清含量。还对60例正常、异常糖耐量 或二型糖尿病的理疗的试验对象进行检测。结构显示，血清丝氨酸蛋白酶抑制剂水平，女性显著高于男性。正常糖耐量组和二型糖尿病患者，血清含量无明显差异。 正常糖耐量组，血清含量和体重指数以及胰岛素的敏感性有显著的相关性。物理锻炼治疗明显增加血清丝氨酸蛋白酶抑制剂水平。肥胖或胰岛素的敏感性异常的患 者，血清含量升高。相反， 二型糖尿病似乎是不存在任何相关性，即高血清浓度的丝氨酸蛋白酶抑制剂、体重超重和降低的胰岛素敏感性。高锻炼指数的观察对象血清丝氨酸蛋白酶抑制剂显示 低水平。对尚未进行物理锻炼的观察进行锻炼训练治疗， 明显升高其丝氨酸蛋白酶抑制剂水平。

北京爱迪博生物科技是专业的脂肪因子研究开发中心，可以为您的糖尿、代谢综合征研究提供有力的技术支持！

 

 

Vaspin serum concentrations in normal glucose tolerant (NGT) individuals and patients with type 2 diabetes (T2D). A: Circulating vaspin in male subjects (n = 36) and female subjects (n = 18) with NGT and in male subjects (n = 53) and female subjects (n = 80) with type 2 diabetes. B: Vaspin serum concentrations in lean (BMI <25 kg/m2; male subjects n = 16; female subjects n = 19), overweight (BMI >25–29.9 kg/m2; male subjects n = 46; female subjects n = 32), and obese (BMI >30 kg/m2; male subjects n = 29; female subjects n = 45) subjects. Data are means ± SE. *P < 0.05 between groups. {blacksquare}, male subjects; {square}, female subjects. Youn BS et al. Diabetes 57:372-377, 2008
Effect of 4 weeks of an intensive exercise program on vaspin serum concentrations in normal glucose tolerant (NGT) individuals and patients with IGT or type 2 diabetes (T2D). Circulating vaspin in groups of NGT (n = 20), IGT (n = 20), and type 2 diabetes (n = 20). Data are means ± SE. *P < 0.05 between baseline and after 4 weeks of intensive physical training. {square}, basal; {blacksquare}, after training. Youn BS et al. Diabetes 57:372-377, 2008
 
Vaspin

vaspin在293T肿瘤细胞、脂肪细胞和前脂肪细胞的表达。Expression of vaspin in 293T cells, adipocytes, and stromal vascular cells. (A) Western blot analysis of mouse vaspin by using supernatants of 293T cultured cells transfected with AxCAmOL64 and polyclonal antivaspin Ab. A prominent band of {approx}45 kDa is observed. (B) Western blots of purified recombinant human and mouse vaspins, derived from E. coli by using pET expression system. (C) Western blot analyses of vaspin by using sera of OLETF and LETO rats, and OLETF rats with EXE, OLETF rats administered TZD and insulin (INS). A major {approx}45-kDa band and a minor {approx}50-kDa band are seen at 30 wk. Band intensity is notably less at 50 wk in OLTEF rats, but it seems to be normalized with insulin and TZD treatments. (D) Expression of vaspin in mature adipocytes and stromal vascular cells isolated from epidydimal (EPI), retroperitoneal (RET), MES, and SUB WATs as analyzed by Northern and Western blot analyses. Expression is confined to adipocytes of visceral WATs and not to stromal endothelial or vascular cells. (E and F) Expression in the adipocytes was confirmed by immunofluorescence microscopy in 30-wk-old OLETF rats. (Scale bars: E, 100 μm; F, 25 μm.) Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10610-5

Vaspin对糖耐量和胰岛素灵敏度的影响。Profiles of glucose tolerance and insulin sensitization tests after administration of vaspin and insulin. (A) Glucose tolerance test. rhVaspin or PBS was i.p. injected into ICR mice fed STD chow or HFHS chow before glucose administration. Glucose levels were significantly reduced with the administration of vaspin (*, P < 0.01). (B) Insulin levels during the glucose tolerance test were unaltered, and HFHS mice remained hyperinsulinemic. (C) Insulin tolerance test. rhVaspin or PBS was i.p. injected into mice before insulin administration. Blood glucose levels were lowered in the HFHS group receiving insulin plus vaspin (*, P < 0.05; **, P < 0.01). All data are mean ± SEM (n = 10). Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10610-5
 

肥胖和二型糖尿病血清丝氨酸蛋白酶抑制剂Vaspin浓度的变化

丝 氨酸蛋白酶抑制剂是十二型糖尿病大鼠腹腔脂肪组织分泌的一个胰岛素增敏性脂肪因子。我们的研究结果显示丝氨酸蛋白酶抑制剂在脂肪组织的表达和肥胖和糖代谢 有关。但是肥胖和二型糖尿病患者血清中丝氨酸蛋白酶抑制剂的含量以及调节变化还不清楚。我们建立了一中酶联免疫定量分析试剂盒分别检测了187例试验观察 对象伴有肥胖、脂肪堆积、胰岛素敏感性和糖耐量异常的血清含量。还对60例正常、异常糖耐量 或二型糖尿病的理疗的试验对象进行检测。结构显示，血清丝氨酸蛋白酶抑制剂水平，女性显著高于男性。正常糖耐量组和二型糖尿病患者，血清含量无明显差异。 正常糖耐量组，血清含量和体重指数以及胰岛素的敏感性有显著的相关性。物理锻炼治疗明显增加血清丝氨酸蛋白酶抑制剂水平。肥胖或胰岛素的敏感性异常的患 者，血清含量升高。相反， 二型糖尿病似乎是不存在任何相关性，即高血清浓度的丝氨酸蛋白酶抑制剂、体重超重和降低的胰岛素敏感性。高锻炼指数的观察对象血清丝氨酸蛋白酶抑制剂显示 低水平。对尚未进行物理锻炼的观察进行锻炼训练治疗， 明显升高其丝氨酸蛋白酶抑制剂水平。
Serum vaspin concentrations in human obesity and type 2 diabetes.
Objective: Vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the regulation of vaspin serum concentrations in human obesity and type 2 diabetes is unknown. Research Design and Methods: For the measurement of vaspin serum concentrations we developed an ELISA. Using this ELISA, we assessed circulating vaspin in a cross-sectional study of 187 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance, or type 2 diabetes (T2D) before and after a 4 weeks physical training program. Results: Vaspin serum concentrations were significantly higher in females as compared to males. There was no difference in circulating vaspin between individuals with NGT and T2D. In the NGT group, circulating vaspin significantly correlated with BMI and insulin sensitivity. Moreover, physical training for 4 weeks resulted in significantly increased circulating vaspin levels. Conclusions: We found a sexual dimorphism in circulating vaspin. Elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity, whereas type 2 diabetes seems to abrogate the correlation between increased circulating vaspin, higher body weight and decreased insulin sensitivity. Low circulating vaspin correlates with a high fitness level, whereas physical training in untrained individuals causes increased vaspin serum concentrations. 
Youn BS, et al. Diabetes. 2007 Nov 8 [Epub ahead of print]
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