Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle.
Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle.
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DOI：
10.1007/s00125-011-2046-3
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发表时间：
2011-05
期刊：
影响因子：
8.2
通讯作者：
Muscat, G. E. O.
中科院分区：
文献类型：
--
作者：
Lau, P.;Fitzsimmons, R. L.;Pearen, M. A.;Watt, M. J.;Muscat, G. E. O.
关键词：
纯合交错（sg/sg）小鼠在所有组织中Rorα（也称为Rora）表达减少且功能失调，表现出瘦弱和血脂异常表型。他们也能抵抗（高脂肪）饮食引起的肥胖。我们探讨了骨骼肌中视黄酸受体相关孤儿受体（ROR）α的作用是否参与了葡萄糖代谢的调节。我们使用了三臂基因组方法，包括表达谱分析，独创性分析和定量PCR验证，以确定骨骼肌中的信号通路，在sg/sg小鼠中受到干扰。此外，Western分析、功能性胰岛素和葡萄糖耐量试验以及离体葡萄糖摄取测定用于表型分析异常v-AKT小鼠胸腺瘤病毒癌基因同源物（AKT）信号传导的影响。纯合子和杂合子（sg/sg和sg/+）动物表现出空腹血糖水平降低，葡萄糖耐量轻度改善和胰岛素敏感性增加。Illumina表达谱和生物信息学分析表明RORα参与代谢疾病和磷脂酰肌醇3-激酶-AKT信号传导。定量PCR和Western分析证实了基础状态下sg/sg小鼠中AKT 2（mRNA和蛋白质）和磷酸化的增加。这与Tbc 1d 1和Glut 4（也称为Slc 2a 4）mRNA和蛋白表达增加有关。最后，与表型一致，我们观察到相对于野生型同窝出生小鼠，sg/sg小鼠骨骼肌中AKT和磷酸化AKT（在基础和胰岛素刺激状态下）以及（离体）葡萄糖摄取的（绝对）水平增加。我们认为Rorα在调节AKT 2信号级联中起重要作用，AKT 2信号级联控制骨骼肌中的葡萄糖摄取。本文的在线版本（doi：10.1007/s 00125 -011-2046-3）包含补充材料，可供授权用户使用。
Homozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Rorα (also known as Rora) expression in all tissues, display a lean and dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) α action in skeletal muscle was involved in the regulation of glucose metabolism. We used a three-armed genomic approach, including expression profiling, ingenuity analysis and quantitative PCR validation to identify the signalling pathway(s) in skeletal muscle that are perturbed in sg/sg mice. Moreover, western analysis, functional insulin and glucose tolerance tests, and ex vivo glucose uptake assays were used to phenotypically characterise the impact of aberrant v-AKT murine thymoma viral oncogene homologue (AKT) signalling. Homozygous and heterozygous (sg/sg and sg/+) animals exhibited decreased fasting blood glucose levels, mildly improved glucose tolerance and increased insulin sensitivity. Illumina expression profiling and bioinformatic analysis indicated the involvement of RORα in metabolic disease and phosphatidylinositol 3-kinase–AKT signalling. Quantitative PCR and western analysis validated increased AKT2 (mRNA and protein) and phosphorylation in sg/sg mice in the basal state. This was associated with increased expression of Tbc1d1 and Glut4 (also known as Slc2a4) mRNA and protein. Finally, in agreement with the phenotype, we observed increased (absolute) levels of AKT and phosphorylated AKT (in the basal and insulin stimulated states), and of (ex vivo) glucose uptake in skeletal muscle from sg/sg mice relative to wild-type littermates. We propose that Rorα plays an important role in regulation of the AKT2 signalling cascade, which controls glucose uptake in skeletal muscle. The online version of this article (doi:10.1007/s00125-011-2046-3) contains supplementary material, which is available to authorised users.
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影响因子：
5.8
作者：
Lang F;Görlach A;Vallon V
通讯作者：
Vallon V
影响因子：
4.8
作者：
Lau, Patrick;Fitzsimmons, Rebecca L.;Muscat, George E. O.
通讯作者：
Muscat, George E. O.
影响因子：
7.7
作者：
Bell, Ming;Wang, Hong;Chen, Hui;McLenithan, John C.;Gong, Da-Wei;Yang, Rong-Zee;Yu, Daozhan;Fried, Susan K.;Quon, Michael J.;Londos, Constantine;Sztalryd, Carole
通讯作者：
Sztalryd, Carole
DOI：
10.1621/nrs.07003
发表时间：
2009
期刊：
Nuclear receptor signaling
影响因子：
--
作者：
Jetten AM
通讯作者：
Jetten AM
影响因子：
64.8
作者：
Hamilton, BA;Frankel, WN;Lander, ES
通讯作者：
Lander, ES