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J Endocrinol. 2016 Oct;231(1):97-108. doi: 10.1530/JOE-16-0349. Epub 2016 Aug 23.

C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis.

Author information

1
Department of Molecular and Cellular BiochemistryKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
2
SKKU Advanced Institute of Nanotechnology and Department of ChemistrySungkyunkwan University, Suwon, Gyeonggi-do, Korea.
3
Department of Obstetrics and GynecologyKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
4
Department of Medical Environmental Biology and Tropical MedicineKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
5
Department of PhysiologyKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
6
Department of Internal MedicineKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea.
7
Department of Molecular and Cellular BiochemistryKangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea ksha@kangwon.ac.kr.

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.

KEYWORDS:

C-peptide; endothelial apoptosis; hyperglycemic memory; reactive oxygen species; vasculopathy

PMID:
27554111
DOI:
10.1530/JOE-16-0349
[Indexed for MEDLINE]

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