The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPARγ–Modulating Activity
Abstract
The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator–activated receptor-γ (PPARγ) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARγ have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARγ; influence the expression of PPARγ target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARγ when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARγ have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.
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Cites
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Global and societal implications of the diabetes epidemic
Zimmet, P., Alberti, K. G. M. M., & Shaw, J. (2001) · Nature · doi:10.1038/414782a · Cited by 5,883
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (2002) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.288.23.2981 · Cited by 5,664
Dahlöf, B., Devereux, R. B., Kjeldsen, S. E., Julius, S., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristiansson, K., Lederballe-Pedersen, O., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08089-3 · Cited by 5,407
The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men
Lakka, H.-M. (2002) · JAMA · doi:10.1001/jama.288.21.2709 · Cited by 5,033
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The mechanisms of action of PPARs
Berger, J., & Moller, D. E. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104018 · Cited by 2,659
McMurray, J. J., Östergren, J., Swedberg, K., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer, M. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14283-3 · Cited by 2,604
Cited by
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system
Mehta, P. K., & Griendling, K. K. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00287.2006 · Cited by 1,924
Luo, Y., Zhao, X., Zhou, J., Yang, J., Zhang, Y., Kuang, W., Peng, J., Chen, L., & Zeng, J. (2017) · Nature Communications · doi:10.1038/s41467-017-00680-8 · Cited by 916
Grundy, S. M. (2016) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2015.10.004 · Cited by 882
Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds
Proschak, E., Stark, H., & Merk, D. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00760 · Cited by 498
Michel, M. C., Foster, C., Brunner, H. R., & Liu, L. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.007278 · Cited by 301
Metadata
- Authors
- Benson, S. C., Pershadsingh, H. A., Ho, C. I., Chittiboyina, A., Desai, P., Pravenec, M., Qi, N., Wang, J., Avery, M. A., & Kurtz, T. W.
- Venue
- Hypertension
- Published
- 2004-05
- Volume
- 43
- Issue
- 5
- Pages
- 993-1002
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2129697991
- Cited by
- 1,073
- References
- 69
- FWCI
- 23.18
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPARγ–Modulating Activity. https://app.cochat.ai/papers/10.1161/01.hyp.0000123072.34629.57
- The paper
- Benson, S. C., Pershadsingh, H. A., Ho, C. I., Chittiboyina, A., Desai, P., Pravenec, M., Qi, N., Wang, J., Avery, M. A., & Kurtz, T. W. (2004). Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPARγ–Modulating Activity. Hypertension. https://doi.org/10.1161/01.hyp.0000123072.34629.57
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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