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World J Diabetes. Dec 15, 2014; 5(6): 912-916
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.912
Possible contribution of (pro)renin receptor to development of gestational diabetes mellitus
Kanako Bokuda, Atsuhiro Ichihara
Kanako Bokuda, Atsuhiro Ichihara, Department of Medicine II, Institute of Endocrinology and Hypertension, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Kanako Bokuda, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
Author contributions: Bokuda K and Ichihara A contributed equally to this work and wrote the paper.
Correspondence to: Kanako Bokuda, MD, Department of Medicine II, Institute of Endocrinology and Hypertension, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. mkanakom31@yahoo.co.jp
Telephone: +81-3-33538111 Fax: +81-3-52697440
Received: July 24, 2014
Revised: August 21, 2014
Accepted: October 23, 2014
Published online: December 15, 2014
Abstract

(Pro)renin receptor [(P)RR], a receptor for renin and prorenin, was first cloned in 2002. Since then, the pathophysiological roles of (P)RR have been growing concerns. (P)RR binds renin and prorenin, with two important consequences, nonproteolytic activation of prorenin, leading to the tissue renin-angiotensin system activation and the intracellular signalings. It is now also known to play an important role as vacuolar H+-ATPase associated protein, involving in Wnt signaling, main component of embryonic development. Extracellular domain of full-length (P)RR is cleaved in golgi-complex forming soluble (P)RR [s(P)RR]. The s(P)RR is now possible to be measured in human blood and urine. It is now measured in different pathophysiological states, and recent study showed that elevated plasma s(P)RR levels in the early stage of pregnancies are associated with higher incidence of gestational diabetes mellitus later in the pregnancies. Plasma s(P)RR levels of neonates are known to be higher than that of adults. It was also shown that, increased s(P)RR concentrations in cord blood, associated with a lower small for gestational age birth likelihood. These data suggests the involvement of (P)RR in embryo’s growth. In this review article, we attempt to figure out the possible pathophysiological roles of the (P)RR in maternal glucose intolerance and embryo’s growth, through reviewing previous studies.

Keywords: (Pro)renin receptor, Gestational diabetes mellitus, Embryonic growth, Renin-angiotensin system, Vacuolar H+-ATPase, Wnt signaling

Core tip: Prorenin receptor [(P)RR] binds (pro)renin, and leads to the activation of tissue renin-angiotensin system and intracellular signalings. It also plays an important role as vacuolar H+-ATPase associated protein, involving in Wnt signaling. Elevated plasma soluble (P)RR [s(P)RR] levels in the early stage of pregnancies are associated with higher incidence of gestational diabetes mellitus (GDM) during the third trimester. Also, elevated s(P)RR levels in cord blood, associated with a lower small for gestational age birth likelihood, suggesting the involvement of (P)RR in embryo’s growth. Here we attempt to elucidate the possible pathophysiological roles of the (P)RR in GDM.