ArticleDiabetes2013
C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 132 citations in OpenAlex.
- The dual role of urinary C-peptide/creatinine ratio: predicting insulin resistance in non-diabetic adults and microvascular complications risk in patients with type 2 diabetes.Frontiers in endocrinology · 2026Article
- Assessment of TG/HDL-C and METS-IR as markers for diabetic retinopathy risk and severity in type 2 diabetes.Frontiers in medicine · 2026Article
- Postprandial C-peptide is more relevant to hemoglobin A1c levels and diabetic microvascular complications than fasting C-peptide in type 2 diabetes.World journal of diabetes · 2025Article
- Article
- Sex-mediated effects of transglutaminase 2 inhibition on endothelial function in human resistance arteries from diabetic and non-diabetic patients.Clinical science (London, England : 1979) · 2025Article
- C-peptide and epicardial adipose tissue in dialysis-dependent chronic kidney disease patients.Frontiers in medicine · 2025Article
- Senescent endothelial cells: a potential target for diabetic retinopathy.Angiogenesis · 2024Review
- Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications.Theranostics · 2024Review
- A Putative NADPH Oxidase Gene in Unicellular PathogenicJournal of fungi (Basel, Switzerland) · 2023Article
- Bioactive Materials for Bone Regeneration: Biomolecules and Delivery Systems.ACS biomaterials science & engineering · 2023Review
- The association of serum C-peptide with the risk of cardiovascular events: a meta-analysis and systematic review.Diabetology & metabolic syndrome · 2023Review
- Urinary c-peptide creatinine ratio (UCPCR) as a predictor of coronary artery disease in type 1 diabetes mellitus.Endocrinology, diabetes & metabolism · 2023Article
- Effects of High Glucose on Human Endothelial Cells Exposed to Simulated Microgravity.Biomolecules · 2023Article
- The role of C-peptide in diabetes and its complications: an updated review.Frontiers in endocrinology · 2023Review
- Therapeutic effect of ultra-long-lasting human C-peptide delivery against hyperglycemia-induced neovascularization in diabetic retinopathy.Theranostics · 2023Article
- High glucose-induced ROS-accumulation in embryo-larval stages of zebrafish leads to mitochondria-mediated apoptosis.Apoptosis : an international journal on programmed cell death · 2022Article
- Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.Bioengineered · 2022Article
- Article
- Midazolam Ameliorates Hyperglycemia-Induced Glomerular Endothelial Dysfunction by Inhibiting Transglutaminase 2 in Diabetes.International journal of molecular sciences · 2022Article
- Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis.Frontiers in physiology · 2022Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C-peptide is a bioactive peptide with a potentially protective role in diabetes complications; however, its molecular mechanism of protection against cardiovascular damage caused by hyperglycemia-induced apoptosis remains unclear. We investigated the protective mechanism of C-peptide against hyperglycemia-induced apoptosis using human umbilical vein endothelial cells and streptozotocin diabetic mice. High glucose (33 mmol/L) induced apoptotic cell death in endothelial cells via sequential elevation of intracellular Ca(2+) and reactive oxygen species (ROS) as well as subsequent activation of transglutaminase 2 (TG2). C-peptide (1 nmol/L) prevented endothelial cell death by inhibiting protein kinase C- and NADPH oxidase-dependent intracellular ROS generation and by abolishing high glucose-induced TG2 activation, without affecting intracellular Ca(2+) levels. Consistently, in the aorta of streptozotocin diabetic mice, hyperglycemia stimulated transamidating activity and endothelial cell apoptosis that was inhibited by C-peptide replacement therapy (35 pmol/min/kg) using osmotic pumps (control and diabetes, n = 8; diabetes + C-peptide, n = 7). In addition, C-peptide prevented hyperglycemia-induced activation of transamidation activity and apoptosis in the heart and renal cortex of streptozotocin diabetic mice. Thus, C-peptide protects endothelial cells from hyperglycemia-induced apoptotic cell death by inhibiting intracellular ROS-mediated activation of TG2. Furthermore, TG2 may be a promising avenue of therapeutic investigation to treat diabetic vasculopathies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.