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

## TL;DR

Stevioside improves glucose uptake in muscle cells by targeting a specific metabolic pathway, suggesting it could help manage type 2 diabetes.

## Contribution

This study reveals a novel mechanism by which stevioside ameliorates glucose metabolism through the PDK4/AMPK/TBC1D1 pathway in muscle cells.

## Key findings

- Stevioside increases glucose uptake by reducing PDK4 and enhancing p-AMPK and TBC1D1 in PA-induced C2C12 myotubes.
- GLUT4 translocation is promoted by stevioside, improving cell membrane glucose transport.
- Overexpression of PDK4 is counteracted by stevioside, supporting its role in glucose regulation.

## Abstract

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.

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.

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.

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.

Stevioside could improve palmitic acid–induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes, supporting the use of SV as a safe natural sweetener in sugar‐free beverages to prevent and control T2DM.