Antidiabetic Properties of Zinc-α2-Glycoprotein in ob/ob Mice
Antidiabetic Properties of Zinc-α2-Glycoprotein in ob/ob Mice
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DOI：
10.1210/en.2009-0827
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发表时间：
2010-03-01
期刊：
影响因子：
4.8
通讯作者：
Tisdale, Michael J.
中科院分区：
文献类型：
--
作者：
Russell, Steven T.;Tisdale, Michael J.
锌-α（2）-糖蛋白（ZAG）是与癌症恶病质中的脂肪损失相关的脂肪因子。本研究的目的是评价重组人ZAG在ob/ob小鼠模型中减轻2型糖尿病的能力。ZAG（50 μ g/d，iv）引起体重进行性减轻（5d内3.5g），对摄食量和饮水量无影响，但体温升高0.4 ℃，提示能量消耗增加。尽管血浆甘油增加，表明脂解增加，但由于肌肉和棕色脂肪组织对葡萄糖和脂质的使用增加，葡萄糖、甘油三酯和非酯化脂肪酸的水平分别降低了17%、25%和62%。后者的重量增加了2倍，解偶联蛋白-1和3的表达增加。血浆胰岛素水平降低了36%，而胰腺胰岛素增加了4倍，葡萄糖耐量试验中葡萄糖曲线下总面积降低了53%，胰岛素需求量降低。由于蛋白质合成增加和蛋白质降解减少，骨骼肌质量增加。这些结果表明，ZAG可能在治疗2型糖尿病方面有效。（内分泌学151：948-957，2010）
Zinc-alpha(2)-glycoprotein (ZAG) is an adipokine associated with fat loss in cancer cachexia. The purpose of this study was to evaluate the ability of recombinant human ZAG to attenuate type 2 diabetes in the ob/ob mouse model. ZAG (50 mu g daily, iv) induced a progressive loss of body weight (3.5g in 5 d), without an effect on food or water intake but with a 0.4 C rise in body temperature, suggesting an increased energy expenditure. Despite an increased plasma glycerol, indicative of increased lipolysis, levels of glucose, triglycerides, and nonesterified fatty acids were decreased by 17, 25, and 62%, respectively, due to an increased use of both glucose and lipids by muscle and brown adipose tissue. The weight of the latter increased 2-fold, and there was increased expression of uncoupling proteins-1 and -3. Plasma insulin levels were reduced by 36%, whereas pancreatic insulin was increased 4-fold, and there was a 53% decrease in the total area under the glucose curve in the glucose tolerance test and reduced insulin requirement. There was an increase in skeletal muscle mass due to an increase in protein synthesis and a decrease in protein degradation. These results suggest that ZAG may potentially be effective in the treatment of type 2 diabetes. (Endocrinology 151: 948-957, 2010)