Stevioside Ameliorates Palmitic Acid–Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes

Abstract

ABSTRACT Background Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. Methods The glucose uptake of C2C12 cells was determined by 2‐NBDG; expression of the Pdk4 gene was measured by quantitative real‐time PCR; and expression of the proteins PDK4, p‐AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. Results In PA‐induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p‐AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4‐overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p‐AMPK and TBC1D1. Conclusion SV was found to ameliorate PA‐induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar‐free beverages to prevent and control T2DM.

Keywords

• glucose metabolism
• PDK4
• stevioside
• sweetener