Civitarese A E, Jenkinson C P, Richardson D, Bajaj M, Cusi K, Kashyap S, Berria R, Belfort R, DeFronzo R A, Mandarino L J, Ravussin E
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Diabetologia. 2004 May;47(5):816-20. doi: 10.1007/s00125-004-1359-x. Epub 2004 Apr 23.
AIMS/HYPOTHESIS: The recent discovery of two adiponectin receptors (AdipoR1 and AdipoR2) will improve our understanding of the molecular mechanisms underlying the insulin-sensitising effect of adiponectin. The aim of this study was to determine for the first time whether skeletal muscle AdipoR1 and/or AdipoR2 gene expression levels are associated with insulin resistance.
Using RT-PCR and northern analysis we measured AdipoR1 and AdipoR2 gene expression in skeletal muscle from healthy Mexican Americans with normal glucose tolerance who had (n=8) or did not have (n=10) a family history of Type 2 diabetes.
Gene expression profiling indicated that the AdipoR1 and AdipoR2 isoforms are highly expressed in human skeletal muscle, unlike in mice where AdipoR2 expression was highest in the liver, and AdipoR1 was highest in skeletal muscle. In the study subjects, the expression levels of AdipoR1 (p=0.004) and AdipoR2 (p=0.04), as well as plasma adiponectin concentration (p=0.03) were lower in people with a family history of Type 2 diabetes than in those with no family history of the disease. Importantly, the expression levels of both receptors correlated positively with insulin sensitivity (r=0.64, p=0.004 and r=0.47, p=0.048 respectively).
CONCLUSIONS/INTERPRETATION: Collectively, these data indicate that both isoforms of the adiponectin receptor play a role in the insulin-sensitising effect of adiponectin.
目的/假设:近期发现的两种脂联素受体(脂联素受体1和脂联素受体2)将增进我们对脂联素胰岛素增敏作用潜在分子机制的理解。本研究的目的是首次确定骨骼肌中脂联素受体1和/或脂联素受体2的基因表达水平是否与胰岛素抵抗相关。
我们采用逆转录聚合酶链反应(RT-PCR)和Northern印迹分析,测量了葡萄糖耐量正常的健康墨西哥裔美国人骨骼肌中脂联素受体1和脂联素受体2的基因表达,这些人中有2型糖尿病家族史(n = 8)或无2型糖尿病家族史(n = 10)。
基因表达谱显示,脂联素受体1和脂联素受体2的亚型在人类骨骼肌中高表达,这与小鼠不同,在小鼠中脂联素受体2在肝脏中表达最高,而脂联素受体1在骨骼肌中表达最高。在研究对象中,有2型糖尿病家族史的人的脂联素受体1(p = 0.004)和脂联素受体2(p = 0.04)的表达水平以及血浆脂联素浓度(p = 0.03)均低于无该疾病家族史的人。重要的是,两种受体的表达水平均与胰岛素敏感性呈正相关(分别为r = 0.64,p = 0.004和r = 0.47,p = 0.048)。
结论/解读:总体而言,这些数据表明脂联素受体的两种亚型在脂联素的胰岛素增敏作用中均发挥作用。