ArticleScience translational medicine2020
Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Sitagliptin, a DPP-4 Inhibitor, Effectively Promotes the Healing of Diabetic Foot Ulcer: A Randomized Controlled Trial.Journal of diabetes · 2025Trial
- Sphingolipid Metabolism: A Pathological Hub Linking Lipid Dysregulation and Chronic Inflammation in Atherosclerotic Cardiovascular Disease.Journal of inflammation research · 2026Review
- Lipoprotein(a) and Vascular Redox State in Patients With Advanced Coronary Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Review
- Sex-specific Associations of Aldosterone and Renin With Body Composition: A Population-based Cohort Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Review
- Perivascular adipose tissue: a central player in the triad of diabetes, obesity, and cardiovascular health.Cardiovascular diabetology · 2024Review
- Intra-operative and post-operative management of conduits for coronary artery bypass grafting: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Surgery and the European Association for Cardio-Thoracic Surgery Coronary Task Force.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2024Review
- Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?Nutrients · 2024Review
- Article
- Effect of dipeptidyl peptidase-4 inhibitor on the progression of coronary artery disease evaluated by computed tomography in patients receiving insulin therapy for type 2 diabetes mellitus.Journal of diabetes · 2023Article
- Article
- Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications.Nature reviews. Cardiology · 2022Review
- Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes.Genetic epidemiology · 2022Article
- RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets.Biomedicines · 2021Article
- DPP4 Activity, Hyperinsulinemia, and Atherosclerosis.The Journal of clinical endocrinology and metabolism · 2021Review
- Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury.JCI insight · 2021Article
- Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia.International journal of molecular sciences · 2021Review
- The renin-angiotensin-aldosterone system as a link between obesity and coronavirus disease 2019 severity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 5 countries.
Funding
Abstract
Recent clinical trials have revealed that aggressive insulin treatment has a neutral effect on cardiovascular risk in patients with diabetes despite improved glycemic control, which may suggest confounding direct effects of insulin on the human vasculature. We studied 580 patients with coronary atherosclerosis undergoing coronary artery bypass surgery (CABG), finding that high endogenous insulin was associated with reduced nitric oxide (NO) bioavailability ex vivo in vessels obtained during surgery. Ex vivo experiments with human internal mammary arteries and saphenous veins obtained from 94 patients undergoing CABG revealed that both long-acting insulin analogs and human insulin triggered abnormal responses of post-insulin receptor substrate 1 downstream signaling ex vivo, independently of systemic insulin resistance status. These abnormal responses led to reduced NO bioavailability, activation of NADPH oxidases, and uncoupling of endothelial NO synthase. Treatment with an oral dipeptidyl peptidase 4 inhibitor (DPP4i) in vivo or DPP4i administered to vessels ex vivo restored physiological insulin signaling, reversed vascular insulin responses, reduced vascular oxidative stress, and improved endothelial function in humans. The detrimental effects of insulin on vascular redox state and endothelial function as well as the insulin-sensitizing effect of DPP4i were also validated in high-fat diet-fed ApoE
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.