Haba Daijiro, Nakagami Gojiro, Minematsu Takeo, Sanada Hiromi
Department of Gerontological Nursing, Wound Care Management, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Tokyo, Japan.
Heliyon. 2021 Sep 7;7(9):e07897. doi: 10.1016/j.heliyon.2021.e07897. eCollection 2021 Sep.
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 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.
糖尿病足溃疡（DFU）愈合延迟是胰岛素抵抗导致高血糖引发血管病变的主要后果之一。改善血液供应和高血糖的干预措施对于治疗DFU至关重要。低频振动（LFV）可促进DFU的外周血流和伤口愈合，不受高血糖影响。我们假设LFV可促进伤口部位脂肪细胞中非胰岛素介导的葡萄糖摄取，即AMPK介导的葡萄糖摄取，从而缓解高血糖，进而加速伤口愈合。本研究的目的是确定能最佳促进脂肪细胞葡萄糖摄取的LFV，并研究LFV增强葡萄糖摄取的潜在机制。本研究使用了3T3-L1脂肪细胞。以50Hz的频率施加LFV，每天40分钟，以研究葡萄糖摄取最有效的振动强度（0-2000mVpp）和持续时间（0-7天）。我们比较评估了对照组和振动组中2-脱氧葡萄糖（2-DG）的摄取情况。为阐明LFV诱导2-DG摄取的潜在机制，分别使用渥曼青霉素和化合物C抑制胰岛素介导的GLUT4易位和AMPK激活。此外，使用免疫荧光图像分析评估GLUT4向质膜的易位情况。我们的结果表明，1000和1500mVpp组的2-DG摄取高于对照组（分别为p=0.0372和0.0018）。在1000mVpp时，5天和7天组的2-DG摄取高于非振动组（分别为p=0.0169和0.0452）。虽然渥曼青霉素不抑制2-DG摄取，但化合物C可以。在用化合物C处理的振动组脂肪细胞中未观察到GLUT4向质膜的易位。因此，我们的结果表明，50Hz、1000mVpp、每天40分钟、持续5天的LFV最适合加速脂肪细胞中AMPK介导的GLUT4易位和葡萄糖摄取。
