apM1在2型糖尿病患者网膜和皮下脂肪组织中的表达降低

M. Statnick, L. Beavers, L. J. Conner, H. Corominola, Dwayne Johnson, C. Hammond, R. Rafaeloff-Phail, T. Seng, T. Suter, J. Sluka, E. Ravussin, R. Gadski, J. Caro
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引用次数: 229

摘要

我们筛选了一个缺失的cDNA文库,以鉴定人类2型糖尿病患者大网膜脂肪组织中的差异表达基因。一个克隆(#1738)显示2型糖尿病患者的网膜脂肪组织明显减少。测序和BLAST分析显示,克隆#1738是脂肪细胞特异性分泌蛋白基因apM1(同义词ACRP30, AdipoQ, GBP28)。与小鼠同源基因一致,apM1 mRNA在培养的人脂肪细胞中表达,而在脂肪前细胞中不表达。通过RT-PCR,我们证实肥胖2型糖尿病患者大网膜脂肪组织中的apM1 mRNA水平与瘦和肥胖血糖正常的受试者相比显著降低。虽然不太明显,但apM1 mRNA水平在2型糖尿病患者的皮下脂肪组织中降低。尽管apM1的生物学功能目前尚不清楚,但在肥胖2型糖尿病患者中观察到的组织特异性表达、与TNFα的结构相似性以及表达失调表明,该因子可能在胰岛素抵抗和2型糖尿病的发病机制中发挥作用。
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Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes
We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.
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