Insulin therapy regulates expression of nitric oxide synthase isoforms in the penis and major pelvic ganglia in diabetic rats

Tarek M. Ahdel-Bakv, Hung T. Hiiynh, Louis R. Begin, Raouf M. Seyam, Mahmoud Abdel-Gawad, Howard Lieberman, Gerald B. Brock

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Erectile dysfunction is a common sequela of diabetes mellitus, 35-75% of diabetic men develop impotence. Insulin is considered the cornerstone of diabetic management. In the present study we investigated the effect of experimentally induced diabetes on erection. This was achieved by electric field stimulation (EPS) of the cavernous nerve. Nitric oxide synthase isoforms (nNOS and eNOS) and their mRNA contents in the penis and MPG in uncontrolled diabetic rats were compared to insulin treated and normal control groups. Male Sprague-Dawley rats (n=80) weighing (300-400gm) were divided into four groups (n=20 each). Diabetes was induced in the first three groups by streptozotocin 60mg/kg in saline phosphate buffer injected intraperitoneally. The first group was uncontrolled diabetics, while the second was fully insulin treated and the third was partially insulin treated. Groups two and three each received daily subcutaneous insulin injection lU/100gm and 0.5U/100gm respectively. The fourth group served as normal non-diabetic control. After eight weeks, 5 rats from each group were subjected to EPS of the cavernous nerve and assessment of the rise in the intracavernous pressure (ICP). The contents of eNOS and nNOS isoforms with their mRNA were determined by western and northern blotting bioassays. Immunohistochemical staining and histopathological examination were performed. Rises in ICP were found to be proportional to diabetic control. Uncontrolled diabetic animals had a rise in ICP of 53.9±6.1 cm H2O, in insulin treated 80.717.6 whereas normal controls recorded a rise of 92.3±10.9. Western blot analysis revealed that nNOS levels were elevated in diabetic penises compared to control and returned to normal following insulin therapy. Similar nNOS mRNA levels were observed in both diabetics and control, however insulin negatively regulated nNOS gene transcription. While northern blotting showed that eNOS mRNA was lower in the penis than in the MPG and there was no change in its level between the different groups. Western blotting demonstrated that penile eNOS was 4 to 5 fold greater than MPG and full insulin therapy upregulated its level by 2 to 3 fold. Insulin therapy improves erection in diabetic rats mainly through its regulatory effect on the translation of nNOS and eNOS in the penis and MPG with little effect on the transcription of their mRNA.

Original languageEnglish (US)
Number of pages1
JournalBritish Journal of Urology
Issue numberSUPPL. 2
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Urology


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