Diazoxide accelerates wound healing by improving EPC function.
Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Zhang-Peng
ZP
Li
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Ru-Juan
RJ
Xin
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Hong
H
Yang
Department of Pharmacy, Zhejiang Xiaoshan Hospital, Zhejiang 311202, China.
Guo-Jun
GJ
Jiang
Department of Pharmacy, Zhejiang Xiaoshan Hospital, Zhejiang 311202, China.
Ya-Ping
YP
Deng
Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Dong-Jie
DJ
Li
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China and Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China, fumingshen@tongji.edu.cn.
Fu-Ming
FM
Shen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003981:Diazoxide / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019700:Thrombospondin 1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D015221:Potassium Channels; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; C585483:Thbs1 protein, mouse; D005947:Glucose; D003981:Diazoxide