title: Proinsulin C-peptide prevents impaired wound healing by activating angiogenesis in diabetes.
abstract: Diabetes mellitus disrupts wound repair and leads to the development of chronic wounds, likely due to impaired angiogenesis. We previously demonstrated that human proinsulin C-peptide can protect against vasculopathy in diabetes; however, its role in impaired wound healing in diabetes has not been studied. We investigated the potential roles of C-peptide in protecting against impaired wound healing by inducing angiogenesis using streptozotocin-induced diabetic mice and human umbilical vein endothelial cells. Diabetes delayed wound healing in mouse skin, and C-peptide supplement using osmotic pumps significantly increased the rate of skin wound closure in diabetic mice. Furthermore, C-peptide induced endothelial cell migration and tube formation in dose-dependent manners, with maximal effect at 0.5 nM. These effects were mediated through activation of extracellular signal-regulated kinase 1/2 and Akt, as well as nitric oxide formation. C-peptide-enhanced angiogenesis in vivo was demonstrated by immunohistochemistry and Matrigel plug assays. Our findings highlight an angiogenic role of C-peptide and its ability to protect against impaired wound healing, which may have significant implications in reparative and therapeutic angiogenesis in diabetes. Thus, C-peptide replacement is a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Young-Cheol
authors.initials: YC
authors.lastname: Lim
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Mahendra Prasad
authors.initials: MP
authors.lastname: Bhatt
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Kwon
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: SungHun
authors.initials: S
authors.lastname: Na
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Molecular and Cellular Biochemistry and Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea. Electronic address: ksha@kangwon.ac.kr.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012883:Skin Ulcer / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002096:C-Peptide