Journal of Investigative Dermatology 2015-01-01

Proinsulin C-peptide prevents impaired wound healing by activating angiogenesis in diabetes.

Young-Cheol Lim, Mahendra Prasad Bhatt, Mi-Hye Kwon, Donghyun Park, SungHun Na, Young-Myeong Kim, Kwon-Soo Ha

Index: J. Invest. Dermatol. 135(1) , 269-78, (2014)

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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.