Journal of Andrology
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Published-Ahead-of-Print February 21, 2007, DOI:10.2164/jandrol.106.001602

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Metformin Restores the Penile Expression of Nitric Oxide Synthase in High Fat-Fed Obese Rats

Yong-Woon Kim , So-Young Park , Jong-Yeon Kim , Jung-Yoon Huh , Woo-Sung Jeon , Chang-Jun Yoon , Sung-Su Yun , and Ki-Hak Moon *

* To whom correspondence should be addressed. E-mail: khmoon{at}med.yu.ac.kr.

Obesity is a well known risk factor for erectile dysfunction, which is associated with a reduced penile nitric oxide synthase (NOS) expression. Recently, it was reported that metformin activates AMP-activated protein kinase (AMPK), which increases the expression of neuronal (n) NOS and endothelial (e) NOS. Thus, to evaluate whether metformin restores NOS expression in penile tissue, we measured penile expression of nNOS and eNOS after four weeks of metformin treatment (300 mg/kg/day) in 4 months (HFO) high fat-fed obese rats. HFO rats have increased fat accumulation in visceral areas and marked suppression of nNOS and eNOS expression in penile tissue. However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue. The levels of AMPK and phospho-AMPK (pAMPK) were also decreased in HFO rats, but were subsequently elevated by metformin treatment. These results suggested that expression of NOS was suppressed by the HF diet, but restored by metformin treatment. The effect of metformin on the expression of NOS may be associated with its activation of AMPK.


Key words: AMP-activated protein kinase • Metformin • nitric oxide synthase • penile tissue






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