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: Mahendra Prasad Bhatt, Yeon-Ju Lee, Se-Hui Jung, Yong Ho Kim, Jong Yun Hwang, Eun-Taek Han, Won Sun Park, Seok-Ho Hong, Young-Myeong Kim, Kwon-Soo Ha
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 231 Issue 1 Pg. 97-108 (10 2016) ISSN: 1479-6805 [Electronic] England
• PMID: 27554111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Society for Endocrinology.

Chemical References

• C-Peptide
• Hypoglycemic Agents
• Insulin
• Protective Agents
• Reactive Oxygen Species
• Shc1 protein, mouse
• Src Homology 2 Domain-Containing, Transforming Protein 1
• Peroxynitrous Acid

Topics

• Animals
• Apoptosis (drug effects)
• C-Peptide (pharmacology)
• Diabetes Mellitus, Experimental (complications, drug therapy)
• Endothelium, Vascular (drug effects)
• Genes, p53 (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Hyperglycemia (drug therapy, etiology)
• Hypoglycemic Agents (pharmacology)
• Insulin (pharmacology)
• Mice
• Peroxynitrous Acid (metabolism)
• Protective Agents (pharmacology)
• Reactive Oxygen Species (metabolism)
• Src Homology 2 Domain-Containing, Transforming Protein 1 (drug effects)