ArticleInternational journal of molecular medicine2016
Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase.
Article in International journal of molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study.International journal of molecular sciences · 2025Trial
- Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy.Vascular medicine (London, England) · 2017Trial
- The role of melatonin in attenuation of vascular endothelin-1 reactivity via calcium channels and endothelial derived relaxing factors in STZ-induced diabetic aortic rats.Journal of muscle research and cell motility · 2026Article
- Incretin-based therapy: a new horizon in diabetes management.Journal of diabetes and metabolic disorders · 2024Review
- The role of low-carbohydrate, high-fat diet in modulating autophagy and endoplasmic reticulum stress in aortic endothelial dysfunction of metabolic syndrome animal model.Frontiers in nutrition · 2024Article
- Insights into the Therapeutic uses of Plant Derive Phytocompounds onDiabetic Nephropathy.Current diabetes reviews · 2024Review
- Thalidomide and a Dipeptidyl Peptidase 4 Inhibitor in a Rat Model of Experimental Autoimmune Myocarditis.Korean circulation journal · 2023Article
- Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease-Pathophysiology and Translational Therapeutic Approaches.Biomedicines · 2023Review
- Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease.Pharmaceutics · 2023Review
- Evaluation of anti-atherosclerotic effects of Sitagliptin via modulation of the mTOR pathway in male rabbits.Journal of medicine and life · 2023Article
- DPP4 as a Potential Candidate in Cardiovascular Disease.Journal of inflammation research · 2022Review
- Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies.Clinical pharmacology and therapeutics · 2022Article
- Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice.Scientific reports · 2021Article
- Sitagliptin attenuates endothelial dysfunction independent of its blood glucose controlling effect.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Effects of sitagliptin on ß-adrenoceptor mediated relaxation in streptozotocin-diabetic rat aortaTurkish journal of medical sciences · 2021Article
- Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging.Frontiers in endocrinology · 2021Review
- Ginsenoside Rb1 Ameliorates Diabetic Arterial StiffeningFrontiers in pharmacology · 2021Article
- Metformin prevents the development of monocrotaline-induced pulmonary hypertension by decreasing serum levels of big endothelin-1.Experimental and therapeutic medicine · 2020Article
- Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.American journal of physiology. Endocrinology and metabolism · 2019Article
- Effect of Saxagliptin on Endothelial Function in Patients with Type 2 Diabetes: A Prospective Multicenter Study.Scientific reports · 2019Article
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9 authors at 1 institution in 1 country.
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Abstract
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP‑1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM). In the present study, the rats were randomly divided into the following four groups: i) control; ii) DM; iii) DM + low‑dose sitagliptin (10 mg/kg); and iv) DM + high‑dose sitagliptin (30 mg/kg). Apart from the control group, all the rats received a high-fat diet for 8 weeks prior to the induction of diabetes with an intraperitoneal injection of streptozotocin. The treatments were then administered for 12 weeks. The serum levels of ET-1, NO, GLP-1 and insulin were measured as well as endothelial function. The expression of ET-1, AMP-activated protein kinase (AMPK) and nuclear factor (NF)-κB/IκBα were determined. After 12 weeks of treatment, the diabetic rats receiving sitagliptin showed significantly elevated serum levels of GLP-1 and NO, and reduced levels of ET-1. Moreover, sitagliptin significantly attenuated endothelial dysfunction as well as the remodeling of the aortic wall. Notably, sitagliptin inhibited ET-1 expression at the transcriptional and translational level in the aorta, which may have been mediated by the suppression of the NF-κB/IκBα system induced by AMPK activation. The majority of the above-mentioned effects were dose dependent. Taken together, the findings of the present study indicate that sitagliptin inhibits ET-1 expression in the aortic endothelium by suppressing the NF-κB/IκBα system through the activation of the AMPK pathway in diabetic rats. These findings further demonstrate some of the vasoprotective properties of DPP-4 inhibitors in vivo.
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