Piezo1 mediates calcium ion influx, glucose transporter 4 translocation, and glucose uptake in adipocytes under low-frequency vibration

Abstract

Diabetic foot ulcers (DFUs) are associated with a high risk of amputation and mortality, necessitating effective wound-healing interventions. Low-frequency vibration (LFV) therapy promotes wound healing by increasing glucose metabolism; however, the mechanisms underlying the effects of LFV on glucose metabolism remain unclear. This study aimed to investigate the role of Piezo1 in glucose uptake induced by LFV in adipocytes. 3T3-L1 adipocytes were subjected to LFV (52 Hz, 600–1,000 mVpp, and 40 min/day) for five days. Cells were divided into non-LFV and LFV groups, both with or without the Piezo1 inhibitor, which was evaluated for intracellular (Ca²⁺) fluorescence intensity, glucose transporter 4 (GLUT4) localization, and glucose uptake. The increased intracellular Ca²⁺ fluorescence intensity induced by LFV was significantly attenuated when combined with Piezo1 inhibitor (p < 0.0001). LFV-induced GLUT4 translocation to the plasma membrane was canceled, and glucose uptake was significantly decreased in the LFV group treated with Piezo1 inhibitor (p < 0.001) compared to the LFV group without Piezo1 inhibitor. The activation of Piezo1 by LFV may lead to a cascade involving Ca²⁺ influx, GLUT4 translocation, and increased glucose uptake. These findings suggest that Piezo1 plays a critical role in promoting the glucose uptake induced by LFV in adipocytes.