(Pro)renin receptor and insulin resistance: possible roles of angiotensin II-dependent and -independent pathways.
A growing body of evidence has suggested the potential role of (pro)renin receptor [(P)RR] in the pathogenesis of cardiovascular and renal injuries during the development of hypertension and diabetes. However, there is very little information on the contribution of (P)RR to the pathophysiology of insulin resistance. In this regard, our preliminary data showed that the development of insulin resistance was associated with nonproteolytic activation of prorenin as well as local angiotensin II generation in skeletal muscle and adipose tissues of obese Otsuka Long-Evans Tokushima Fatty rats. In fructose-fed rats, insulin resistance was also associated with nonproteolytic activation of prorenin and skeletal muscle angiotensin II generation. Furthermore, inhibition of (P)RR with handle region decoy peptide (HRP) improved the development of fructose-induced insulin resistance. However, in other animal model, such as transgenic rats overexpressing the human renin gene, HRP failed to ameliorate glucose intolerance. In this review, we will summarized the current knowledge regarding the possible contribution of (P)RR to the pathophysiology of insulin resistance.
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Kazi
K
Rafiq
Hirohito
H
Mori
Tsutomu
T
Masaki
Akira
A
Nishiyama
D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
D000804:Angiotensin II; D009842:Oligopeptides; D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C527127:handle-region peptide, rat; C514240:ATP6AP2 protein, rat