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

被引:44
作者
Nagai, Yukiko [2 ]
Ichihara, Atsuhiro [4 ,5 ]
Nakano, Daisuke [1 ]
Kimura, Shoji [1 ]
Pelisch, Nicolas [3 ]
Fujisawa, Yoshihide [2 ]
Hitomi, Hirofumi [1 ]
Hosomi, Naohisa [3 ]
Kiyomoto, Hideyasu [3 ]
Kohno, Masakazu [3 ]
Ito, Hiroshi [4 ,5 ]
Nishiyama, Akira [1 ]
机构
[1] Kagawa Univ, Dept Pharmacol, Kita Ku, Kagawa 7610793, Japan
[2] Kagawa Univ, Life Sci Res Ctr, Kagawa 7610793, Japan
[3] Kagawa Univ, Dept Cardiorenal & Cerebrovasc Med, Kagawa 7610793, Japan
[4] Keio Univ, Sch Med, Dept Antiaging Med & Endocrinol, Tokyo, Japan
[5] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan
关键词
TYPE-2; DIABETIC-RATS; END-POINT REDUCTION; CARDIOVASCULAR MORBIDITY; LOSARTAN INTERVENTION; RECEPTOR BLOCKERS; RANDOMIZED-TRIAL; ADIPOSE-TISSUE; HANDLE-REGION; HYPERTENSION; EXPRESSION;
D O I
10.1113/expphysiol.2009.048108
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:1016 / 1023
页数:8
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