α2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans
α2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans
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DOI：
10.2337/diacare.29.04.06.dc05-1938
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发表时间：
2006-04-01
期刊：
影响因子：
16.2
通讯作者：
Häring, HU
中科院分区：
文献类型：
--
作者：
Stefan, N;Hennige, AM;Häring, HU
目的 - α(2)-Heremans-Schmid 糖蛋白（动物中的 AHSG 胎球蛋白-A）会损害体外和啮齿动物体内的胰岛素信号传导。 AHSG 是否与人类胰岛素抵抗有关正在研究中。在饮食引起的肥胖（通常与肝脂肪变性相关）的动物模型中，观察到肝脏中 Ahsg mRNA 表达增加。因此，我们推测，人类肝脏专门分泌的 AHSG 血浆蛋白可能不仅与胰岛素抵抗有关，而且还与肝脏中的适当积累有关。 研究设计和方法 - 横断面分析纳入了来自 106 名没有 2 型糖尿病的健康白种人的数据。一个由 47 人组成的小组拥有来自纵向研究的数据。通过正常血糖-高胰岛素钳夹测量胰岛素敏感性，并通过 H-1 磁共振波谱法测定肝脏脂肪。 结果 - 根据年龄、性别和体脂百分比调整后，糖耐量受损受试者的 AHSG 血浆水平高于糖耐量正常受试者 (P = 0.006)。在横断面分析中，AHSG 血浆水平与胰岛素敏感性呈负相关（r = -0.22，P = 0.03）。此外，它们与肝脏脂肪呈正相关（r = 0.27，P = 0.01）。在纵向分析中，体重减轻时，肝脏脂肪的减少伴随着 AHSG 血浆浓度的降低。此外，基线时高 AHSG 水平预示胰岛素敏感性增加较少 (P = 0.02)。 结论 - 我们发现高 AHSG 血浆水平与人类胰岛素抵抗相关。此外，肝脏脂肪堆积的受试者中，AHSG 血浆水平升高。这与 AHSG 作为脂肪肝和胰岛素抵抗之间联系的潜在作用是一致的。
OBJECTIVE - The alpha(2)-Heremans-Schmid glycoprotein (AHSG Fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated With insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in Ahsg mRNA expression was observed in the liver. Therefore, we hypothesized that the AHSG plasma protein, which is exclusively secreted by the liver in humans, may not only be associated with insulin resistance but also with fit accumulation in the liver.RESEARCH DESIGN AND METHODS - Data from 106 healthy Caucasians without type 2 diabetes were included in cross-sectional analyses. A subgroup of 47 individuals had data from a longitudinal study. Insulin sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat was determined by H-1 magnetic resonance spectroscopy.RESULTS - AHSG plasma levels, adjusted for age, sex, and percentage of body fat, were higher in subjects with impaired glucose tolerance compared with subjects with normal glucose tolerance (P = 0.006). AHSG plasma levels were negatively associated with insulin sensitivity (r = -0.22, P = 0.03) in cross-sectional analyses. Moreover, they were positively associated with liver fat (r = 0.27, P = 0.01). In longitudinal analyses, Under weight loss, a decrease in liver fat was accompanied by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at baseline predicted less increase in insulin sensitivity (P = 0.02).CONCLUSIONS - We found that high AHSG plasma levels are associated with insulin resistance in humans. Moreover, AHSG plasma levels are elevated in subjects with fat accumulation in the liver. This is consistent with a potential role of AHSG as a link between fatty liver and insulin resistance.