ArticlePloS one2013
Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 100 citations in OpenAlex.
- Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial.International journal of obesity (2005) · 2015Trial
- Atrial fibroblast metabolic reprogramming in atrial fibrillation: a candidate mechanism within multicellular atrial cardiomyopathy.Frontiers in cardiovascular medicine · 2026Review
- GLP-1 receptor agonist protects glucose-stimulated insulin secretion in pancreatic β-cells against lipotoxicity via PPARδ/UCP2 pathway.Cellular and molecular life sciences : CMLS · 2025Article
- The role of myocardial fibrosis in the diabetic cardiomyopathy.Diabetology & metabolic syndrome · 2025Review
- Sitagliptin, diabetes mellitus, and heart failure: an in-depth review of sitagliptin therapy and heart failure in patients with diabetes mellitus.Diabetology international · 2025Review
- Immunomodulatory Effect of Rivaroxaban Nanoparticles Alone and in Combination with Sitagliptin on Diabetic Rat Model.Diseases (Basel, Switzerland) · 2025Article
- Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.Biomedicines · 2024Review
- Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities.International journal of molecular sciences · 2024Review
- Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective.Pharmaceuticals (Basel, Switzerland) · 2023Review
- An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis.International journal of molecular sciences · 2023Review
- Guidelines on models of diabetic heart disease.American journal of physiology. Heart and circulatory physiology · 2022Review
- Endogenous Protective Factors and Potential Therapeutic Agents for Diabetes-Associated Atherosclerosis.Frontiers in endocrinology · 2022Review
- SARS-CoV-2 and diabetes: A potential therapeutic effect of dipeptidyl peptidase 4 inhibitors in diabetic patients diagnosed with COVID-19.Metabolism open · 2021Article
- Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities.Advanced drug delivery reviews · 2021Review
- Experimental animal models for diabetes and its related complications-a review.Laboratory animal research · 2021Review
- Positioning Metabolism as a Central Player in the Diabetic Heart.Journal of lipid and atherosclerosis · 2020Review
- DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?Frontiers in pharmacology · 2020Review
- Cardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Disease.International journal of molecular sciences · 2019Article
- Voltage dependence of the CaMolecular and cellular biochemistry · 2018Article
- The pleiotropic cardiovascular effects of dipeptidyl peptidase-4 inhibitors.British journal of clinical pharmacology · 2018Review
Corrections and comments
- Erratum issuedAres-Carrasco, Sara [added]
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.
methodsGoto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.
resultsUntreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.
conclusionsSitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.
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