Transcriptome Changes of Skeletal Muscle RNA-Seq Speculates the Mechanism of Postprandial Hyperglycemia in Diabetic Goto-Kakizaki Rats During the Early Stage of T2D

Abstract

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, Tbc1d4, 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. Pdk4, 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 (Acadl, Acsl1 and Fabp4) 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 Tbc1d4, Pdk4, Acadl, Acsl1 and Fabp4 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 (Tbc1d4, Pdk4, Acadl, Acsl1 and Fabp4) 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. Tbc1d4, Acadl, Acsl1 and Fabp4 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.

Keywords

• skeletal muscle
• type 2 diabetes (T2D)
• Goto-Kakizaki (GK) rats
• postprandial hyperglycemia
• RNA-Seq