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Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin–angiotensin system

TheodoreW. Kurtza and Michal Pravenecb

Several lines of evidence suggest that angiotensinconverting enzyme (ACE) inhibitors and some angiotensin II receptor blockers (ARBs) may improve insulin sensitivity and decrease the risk for type 2 diabetes. It is widely assumed that the potential antidiabetic properties of these agents are largely mediated by their ability to interfere with the adverse metabolic effects of angiotensin II. However, recent studies suggest that ACE inhibitors might improve glucose metabolism primarily through effects on kinin- nitric oxide pathways.

In addition, one ARB in particular, telmisartan, has been found to effectively activate the peroxisome proliferator activated receptor gamma (PPAR), a well-known target for insulin-sensitizing, antidiabetic drugs. Thus, the beneficial metabolic effects of some ACE inhibitors and ARBs may go well beyond their effects on the renin-angiotensin system. Moreover, the identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR modulating ability suggests new opportunities for developing thirdgeneration ARBs and PPAR activators, with enhanced potential for treating hypertension, diabetes and the metabolic syndrome. J Hypertens 22:2253-2261 & 2004 Lippincott Williams & Wilkins. Journal of Hypertension 2004, 22:2253-2261

Keywords: angiotensin II, angiotensin II receptors, renin-angiotensin system, metabolic syndrome, diabetes, insulin resistance, peroxisome proliferator activated receptors, thiazolidinediones, telmisartan

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