KLF3 impacts insulin sensitivity and glucose uptake in skeletal muscle

• DOI: 10.1152/ajpcell.00085.2024
• Publication Date: 2024-09-09T21:08:43Z
• Authors: Shuying Fu; Xiaocheng Gong; Keying Liang; Ke Ding; Li Qiu; Huice Cen; Hongli Du
• Keywords: GLUT4; Carbohydrate Metabolism

Skeletal muscle is one of the predominant sites involved in glucose disposal, accounting for approximately 80% postprandial uptake, and plays a critical role maintaining glycemic homeostasis. Dysregulation energy metabolism skeletal developing insulin resistance type 2 diabetes (T2D). Transcriptomic responses to exercise found that expression Klf3 was increased T2D Goto-Kakizaki (GK) rats decreased after with improved hyperglycemia resistance, implying might be associated sensitivity metabolism. We also knockdown promoted basal insulin-stimulated uptake L6 myotubes, while overexpression resulted opposite. Through pairwise comparisons myotubes transcriptome, we identified 2256 1988 differentially expressed genes groups, respectively. In signaling, Slc2a4, Akt2, Insr Sorbs1 significantly by klf3 overexpression; Ptprf Fasn were markedly downregulated reduced group upregulated overexpressed group. Moreover, downregulation GLUT4 AKT proteins, as well translocation cell membrane situation, enhanced sensitivity, characterized AKT, TBC1D1 TBC1D4 phosphorylation, showed contrary results. These results suggest affects via signal transduction intracellular metabolism, offering novel potential treatment strategy T2D.