title: Possible contribution of the non-proteolytic activation of prorenin to the development of insulin resistance in fructose-fed rats.
abstract: Recent studies have shown that blocking non-proteolytically activated prorenin with a decoy peptide for the handle region of the prorenin prosegment (HRP) inhibits the development of microvascular complications in diabetic animals. In the present study, we investigated whether non-proteolytic activation of prorenin contributes to the development of fructose-induced insulin resistance. Rats were fed a standard diet (n = 10), a 60% high fructose diet (n = 16), or a high fructose diet + HRP (0.1 mg kg(-1) day(-1), n = 16) for 10 weeks. Fructose-fed rats showed higher systolic blood pressure (SBP), fasting plasma triglycerides, total cholesterol and insulin levels; which, except for SBP, were suppressed by HRP. The responses of plasma glucose and insulin levels to oral glucose loading were significantly greater in fructose-fed rats than in standard diet-fed rats. The HRP normalized the enhanced responses of plasma glucose and insulin levels that were observed in fructose-fed rats. Moreover, HRP suppressed the enhanced prorenin activation and angiotensin II formation in the soleus muscle of fructose-fed rats. These data suggest that local angiotensin II generation in skeletal muscle, induced by non-proteolytic activation of prorenin, contributes to the development of insulin resistance induced by a high fructose diet.
authors.affiliation: Life Sciences Research Center, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nagai
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pelisch
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics; D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000009:adverse effects; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D012083:Renin / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D000093342:Prorenin Receptor
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014280:Triglycerides; C527127:handle-region peptide, rat; D000804:Angiotensin II; D005632:Fructose; D002784:Cholesterol; D012083:Renin; D000093342:Prorenin Receptor