Possible involvement of the (pro)renin receptor-dependent system in the development of insulin resistance.

It is widely acknowledged that activation of the renin-angiotensin system impairs insulin sensitivity. Pharmacological inhibition of the (pro)renin receptor-dependent system has shown beneficial effects in diabetic nephropathy, retinopathy and hypertensive cardiac damage in animal models. Previously, we showed that fructose feeding stimulated nonproteolytic activation of prorenin and subsequent production of angiotensin II in skeletal muscle in rats, and that inhibition of the (pro)renin receptor-dependent system improved the development of fructose feeding-induced insulin resistance. In addition, our current preliminary study suggests that local angiotensin II generation in skeletal muscle and adipose tissues induced by nonproteolytic activation of prorenin is involved in the development of spontaneous insulin resistance in type 2 diabetic rats. In this review, we will briefly summarize the possible contribution of the (pro)renin receptor-dependent system to the pathogenesis of insulin resistance, with a focus on how the nonproteolytic activation of prorenin contributes to the development of insulin resistance.