Angiotensin-receptor blocking agents and the peroxisome proliferator-activated receptor-γ system
The metabolic syndrome leads to cardiovascular disease and type 2 diabetes mellitus, through multiple risks, such as insulin resistance, dyslipidemia, hyperinsulinemia, and hypertension. It also represents a disorder of partial genetic background as mutations of the peroxisome proliferator-activated receptor-gamma (PPAR-γ). Thiazolidinedione agonists for the PPAR-γ system are effective in control of insulin resistance and diabetes. Telmisartan has a molecular structure that imparts partial agonist properties with the PPAR-γ molecule, which results in reductions in glucose and lipid metabolism. Administration of telmisartan to rats on a high-fat, high-carbohydrate diet leads to reductions in glucose, insulin, and triglyceride levels. The results imply that the ARB agent, telmisartan, could treat both the hemodynamic and metabolic aberrations seen in subjects with the metabolic syndrome, such as insulin resistance, glucose intolerance, and hypertension.
Unable to display preview. Download preview PDF.
References and Recommended Reading
- 1.Benson SC, Pershadsingh HA, Ho CL, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-gamma-modulating activity. Hypertension 2004, 43:993–1002. The first paper to show structural similarity between telmisartan and the PPAR-gamma system, its effect on adipogenesis, and its ability to reduce metabolic dysfunction in rats with the metabolic syndrome.PubMedCrossRefGoogle Scholar
- 2.Schupp M, Janke J, Clasen R, et al.: Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptorgamma activity. Circulation 2004, 109:2054–2057. This study confirmed the effect of telmisartan and, to a lesser extent, irbesartan on adipocyte differentiation. Most importantly, by using an AT1 receptor-deficient model, they showed that the effect of ARB agents on PPAR-γ was independent of angiotensin II AT1 receptor binding.PubMedCrossRefGoogle Scholar
- 5.Derosa G, Cicero AF, Bertone G, et al.: Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized, double-blind study. Clin Ther 2004, 26:1228–1236.PubMedCrossRefGoogle Scholar
- 6.Derosa G, Rogonesi PD, Mugellini A, et al.: Effects of telmisartan compared with eprosartan in mildly hypertensive, type 2 diabetic patients on blood pressure control, glucose metabolism, and lipid profile: a randomized, double-blind, placebo controlled 12 month study. Hypertens Res 2004, 27:457–464.PubMedCrossRefGoogle Scholar
- 10.Kurtz TW, Pravenec M: Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin angiotensin system. J Hypertens 2004, 22:2253–2261. An excellent review of the comparative metabolic effects of ACE inhibitors and ARBs from basic research to clinical trials.PubMedCrossRefGoogle Scholar