[Frontiers in Bioscience S3, 1478-1485, June 1, 2011]

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

Kazi Rafiq1, Hirofumi Hitomi1, Daisuke Nakano1, Atsuhiro Ichihara2, Akira Nishiyama1

1Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan, 2Anti-Aging Medicine and Endocrinology and Internal Medicine, Keio University School of Medicine, Tokyo, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. RAS and Insulin Resistance
4. Insulin Resistance and the (Pro)renin Receptor-dependent System
5. Clinical Studies
6. Conclusions
7. References

1. ABSTRACT

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.