Skeletal muscle RNA-seq reveals the postprandial hyperglycemia mechanism in T2D Goto-Kakizaki rats during the earlier stage
作者单位：School of Biological and Biological EngineeringSouth China University of Technology
会议名称：《2018中国遗传学会第十次全国会员代表大会暨学术讨论会》
会议日期：2018年
关 键 词：GK rats postprandial hyperglycemia RNA-seq,skeletal muscle T2D
摘 要：It has been reported that isolated impaired glucose tolerance（IGT） was common among diabetes patients in Asian. 46.6% undiagnosed Type 2 diabetes（T2 D） subjects had isolated IGT in China. Skeletal muscle is responsible for 70%-80% postprandial glucose disposal, indicating glucose disposal in skeletal muscle might play an important role in postprandial glucose disposal. Spontaneous non-obese T2 D GotoKakizaki（GK） rats were produced by selective breeding from Wistar rats with IGT. We used GK and Wistar rats aged 3 and 4 weeks to reveal the postprandial hyperglycemia mechanism in GK rats skeletal muscle during the earlier stage of T2 D by RNA-Seq and quantitative Real-Time PCR（RT-qPCR）. In comparison with control Wistar rats, the expression of Pdk4 were significantly increased in GK rats skeletal muscle at 3 and 4 weeks. Previous researches have demonstrated that significantly upregulated Pdk4 could inhibited glucose uptake and glucose oxidation in skeletal muscle. The expression of gene Tbc1 d4 regulating glucose uptake were reduced in GK rats skeletal muscle at 3 and 4 weeks, also suggesting reduced glucose uptake in GK rats skeletal muscle at 3 and 4 weeks. The widely upregulated genes（Acadl, Acsl1, Ech1, Fabp4 and Mlycd） related to fatty acid oxidation in GK rats skeletal muscle at 4 weeks suggested increased fatty acid oxidation. Increased fatty acid oxidation could inhibited glucose oxidation. The reduced glucose uptake, reduced glucose oxidation and increased fatty acid oxidation might be the major reason resulting in the postprandial hyperglycemia in GK rats. Our study provided a theoretical basis for developing therapeutic approaches of isolated impaired glucose tolerance T2 D.