Abstract
Delayed healing of diabetic foot ulcers (DFUs) is one of the major consequences of angiopathy caused by hyperglycemia stemming from insulin resistance. Interventions that improve blood supply and hyperglycemia are essential for treating DFUs. Low-frequency vibration (LFV) promotes peripheral blood flow and wound healing in DFUs, regardless of hyperglycemia. We hypothesized that LFV promotes non-insulin-mediated glucose uptake, which is also referred to as AMPK-mediated glucose uptake, in adipocytes at wound sites, thereby alleviating hyperglycemia, which, in turn, accelerates wound healing. The objective of this in vitro study was to identify LFVs that optimally promote glucose uptake in adipocytes and investigate the mechanism underlying enhanced glucose uptake caused by LFV. 3T3-L1 adipocytes were used in this study. LFV was applied at 50 Hz for 40 min/d to investigate the most effective vibration intensity (0-2000 mVpp) and duration (0-7 d) of glucose uptake. We comparatively assessed 2-deoxyglucose (2-DG) uptake in control and vibration groups. To elucidated the mechanism underlying 2-DG uptake induced by LFV, wortmannin and compound C were used to inhibit insulin-mediated GLUT4 translocation and AMPK activation, respectively. Additionally, GLUT4 translocation to the plasma membrane was assessed using immunofluorescence image analysis. Our results indicated that 2-DG uptake in the 1000 and 1500 mVpp groups was higher than that in the control group (p = 0.0372 and 0.0018, respectively). At 1000 mVpp, 2-DG uptake in the 5- and 7-d groups was higher than that in the non-vibration group (p = 0.0169 and 0.0452, respectively). Although wortmannin did not inhibit 2-DG uptake, compound C did. GLUT4 translocation to the plasma membrane was not observed in the vibration group adipocytes treated with compound C. Thus, our results indicated that an LFV of 50 Hz, 1000 mVpp, 40 min/d, over 5 d was optimal for accelerating AMPK-mediated GLUT4 translocation and glucose uptake in adipocytes.