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MSC attenuate diabetes-induced functional impairment in adipocytes via secretion of insulin-like growth factor-1
Authors:Dongyun Gao  Jiangfan Xie  Junhua Zhang  Changjiang Feng  Bin Yao  Kui Ma  Jiwei Li  Xu Wu  Sha Huang  Xiaobing Fu
Institution:1. Key Laboratory of Wound Repair and Regeneration of PLA, The First Affiliated Hospital, General Hospital of PLA, Beijing 100048, PR China;2. Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China;3. Department of Oncology, Dongtai People’s Hospital, Dongtai 224200, PR China;4. Graduate School of Tianjin Medical University, Tianjin 300052, PR China;5. Department of Thoracic and Cardiovascular Surgery, Peking University People’s Hospital, Peking University, Beijing 100044, PR China;6. Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA, Beijing 100853, PR China;g Hainan Branch of the Chinese PLA General Hospital, Sanya, Hainan Province 572014, PR China
Abstract:The function of subcutaneous adipocytes in promoting wound healing is significantly suppressed in diabetic wounds. Recent studies have demonstrated the ability of mesenchymal stem cell (MSC) to ameliorate impaired diabetic wound healing. We hypothesized that MSC function may involve subcutaneous adipocytes. The abnormal function of subcutaneous adipocytes from STZ induced diabetic mice including glucose uptake and free fatty acid (FFA) secretion level were assessed. Then these cells were co-cultured with MSC via a transwell system to observe the changes of metabolic index and glucose transporter four (GLUT4) as well as phosphoinositide 3-kinase/protein kinase (PI3K/AKT) signaling pathway expression. The results of metabolic index suggest that MSC obviously attenuated the diabetes-induced functional impairment. Both mRNA and protein expression analyses showed that PI3K/AKT insulin signaling pathway and GLUT4 expression were up-regulated. These changes were substantially associated with a increased level of insulin-like growth factor-1 (IGF-1) secretion from MSC. These findings suggest that MSC could attenuate abnormal function of diabetic adipocytes by IGF-1secretion, which was more or less associated with the beneficial effects of MSC on improving diabetic wound healing.
Keywords:MSC  Adipocytes  Conditioned medium (CM)  Wound  IGF-1
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