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 Ito, Akira Nishiyama

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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

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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    Nagai, Y., Ichihara, A., Nakano, D., Kimura, S., Pelisch, N., Fujisawa, Y., Hitomi, H., Hosomi, N., Kiyomoto, H., Kohno, M., Ito, 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, 94(9), 1016-1023. https://doi.org/10.1113/expphysiol.2009.048108