title: C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis.
abstract: C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO(-) and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66(shc) after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO(-) in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage.
authors.affiliation: Department of Molecular and Cellular BiochemistryKangwon 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 BiochemistryKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular BiochemistryKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Se-Hui
authors.initials: SH
authors.lastname: Jung
authors.affiliation: SKKU Advanced Institute of Nanotechnology and Department of ChemistrySungkyunkwan University, Suwon, Gyeonggi-do, Korea.
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and GynecologyKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Jong Yun
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Medical Environmental Biology and Tropical MedicineKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
authors.affiliation: Department of PhysiologyKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Internal MedicineKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Molecular and Cellular BiochemistryKangwon 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 BiochemistryKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea ksha@kangwon.ac.kr.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002096:C-Peptide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D030421:Peroxynitrous Acid / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000187:drug effects
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D020011:Protective Agents; D017382:Reactive Oxygen Species; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D030421:Peroxynitrous Acid
keywords: C-peptide; endothelial apoptosis; hyperglycemic memory; reactive oxygen species; vasculopathy