Possible contribution of the non-proteolytic activation of prorenin to the development of insulin resistance in fructose-fed rats

Yukiko Nagai, Atsuhiro Ichihara, Daisuke Nakano, Shoji Kimura, Nicolas Pelisch, Yoshihide Fujisawa, Hirofumi Hitomi, Naohisa Hosomi, Hideyasu Kiyomoto, Masakazu Kohno, Hiroshi Itoh, Akira Nishiyama

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1016-1023
Number of pages8
JournalExperimental Physiology
Volume94
Issue number9
DOIs
Publication statusPublished - 2009 Sep

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Fructose
Renin
Insulin Resistance
Diet
Insulin
Blood Pressure
Glucose
Angiotensin II
Skeletal Muscle
Diabetes Complications
Fasting
Triglycerides
Cholesterol
Hypertension
Peptides

ASJC Scopus subject areas

  • Physiology

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Possible contribution of the non-proteolytic activation of prorenin to the development of insulin resistance in fructose-fed rats. / Nagai, Yukiko; Ichihara, Atsuhiro; Nakano, Daisuke; Kimura, Shoji; Pelisch, Nicolas; Fujisawa, Yoshihide; Hitomi, Hirofumi; Hosomi, Naohisa; Kiyomoto, Hideyasu; Kohno, Masakazu; Itoh, Hiroshi; Nishiyama, Akira.

In: Experimental Physiology, Vol. 94, No. 9, 09.2009, p. 1016-1023.

Research output: Contribution to journalArticle

Nagai, Y, Ichihara, A, Nakano, D, Kimura, S, Pelisch, N, Fujisawa, Y, Hitomi, H, Hosomi, N, Kiyomoto, H, Kohno, M, Itoh, H & Nishiyama, A 2009, 'Possible contribution of the non-proteolytic activation of prorenin to the development of insulin resistance in fructose-fed rats', Experimental Physiology, vol. 94, no. 9, pp. 1016-1023. https://doi.org/10.1113/expphysiol.2009.048108
Nagai, Yukiko ; Ichihara, Atsuhiro ; Nakano, Daisuke ; Kimura, Shoji ; Pelisch, Nicolas ; Fujisawa, Yoshihide ; Hitomi, Hirofumi ; Hosomi, Naohisa ; Kiyomoto, Hideyasu ; Kohno, Masakazu ; Itoh, Hiroshi ; Nishiyama, Akira. / Possible contribution of the non-proteolytic activation of prorenin to the development of insulin resistance in fructose-fed rats. In: Experimental Physiology. 2009 ; Vol. 94, No. 9. pp. 1016-1023.
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