School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510000, China.
Genes (Basel). 2019 May 28;10(6):406. doi: 10.3390/genes10060406.
To address how skeletal muscle contributes to postprandial hyperglycemia, we performed skeletal muscle transcriptome analysis of diabetic Goto-Kakizaki (GK) and control Wistar rats by RNA sequencing (RNA-Seq). We obtained 600 and 1785 differentially expressed genes in GK rats compared to those Wistar rats at three and four weeks of age, respectively. Specifically, , involved in glucose uptake, was significantly downregulated in the skeletal muscle of GK aged both three and four weeks compared to those of age-matched Wistar rats. , related to glucose uptake and oxidation, was significantly upregulated in the skeletal muscle of GK aged both three and four weeks compared to that of age-matched Wistar rats. Genes (, and ) implicated in fatty acid oxidation were significantly upregulated in the skeletal muscle of GK aged four weeks compared to those of age-matched Wistar rats. The overexpression or knockout of , , , and has been reported to change glucose uptake and fatty acid oxidation directly in rodents. By taking the results of previous studies into consideration, we speculated that dysregulation of key dysregulated genes (, , , and ) may lead to a decrease in glucose uptake and oxidation, and an increase in fatty acid oxidation in GK skeletal muscle at three and four weeks, which may, in turn, contribute to postprandial hyperglycemia. Our research revealed transcriptome changes in GK skeletal muscle at three and four weeks. , , and were found to be associated with early diabetes in GK rats for the first time, which may provide a new scope for pathogenesis of postprandial hyperglycemia.
为了研究骨骼肌如何导致餐后高血糖，我们通过 RNA 测序（RNA-Seq）对糖尿病 Goto-Kakizaki（GK）大鼠和对照 Wistar 大鼠的骨骼肌进行了转录组分析。与 3 周龄 Wistar 大鼠相比，GK 大鼠在 3 周和 4 周龄时分别有 600 个和 1785 个差异表达基因。具体而言，在 3 周和 4 周龄的 GK 大鼠骨骼肌中，与葡萄糖摄取相关的 显著下调。在 3 周和 4 周龄的 GK 大鼠骨骼肌中，与葡萄糖摄取和氧化相关的 显著上调。在 4 周龄的 GK 大鼠骨骼肌中，与脂肪酸氧化相关的基因（、和）显著上调。在 4 周龄的 GK 大鼠骨骼肌中，与脂肪酸氧化相关的基因（、和）显著上调。已经有报道称，在啮齿动物中，过表达或敲除 、 、 、 和 会直接改变葡萄糖摄取和脂肪酸氧化。考虑到之前研究的结果，我们推测关键失调基因（、、、和）的失调可能导致 GK 骨骼肌在 3 周和 4 周时葡萄糖摄取和氧化减少，脂肪酸氧化增加，从而导致餐后高血糖。我们的研究揭示了 GK 骨骼肌在 3 周和 4 周时的转录组变化。首次发现 、 、 和 与 GK 大鼠早期糖尿病有关，这可能为餐后高血糖的发病机制提供了新的研究范围。
