Diabetes induced erectile dysfunction and apoptosis in penile crura are recovered by insulin treatment in rats.
OBJECTIVE
We hypothesized that apoptosis is a downstream event in erectile dysfunction, and pro-apoptotic (Bak and Bax) and anti-apoptotic (Bcl-2 and Bcl-x) factors are involved in the etiology of diabetes induced erectile dysfunction. To test this hypothesis the intracavernous pressure of diabetic and insulin treated rats was measured to assess erectile function. Molecular and immunohistochemical analyses for apoptosis were then performed in rat crura to assess their role in diabetes induced erectile dysfunction and insulin treatment.


METHODS
A total of 70, 6-month-old male Sprague-Dawley rats were divided into 2 groups, including a diabetic (50) and a healthy control (20) group. The diabetic group received intraperitoneal injection of streptozotocin (STZ) (Sigma-Aldrich Co., St. Louis, Missouri) to induce diabetes. Subcutaneous injection of insulin was administered daily to 9 diabetic rats 4 and 8 weeks after STZ injections for 4 and 8 weeks, respectively. Functional studies were performed in 9 diabetic rats each 4, 8 and 12 weeks after STZ injections, in 6 age matched control rats and in insulin treated rats at the termination of therapy. After the completion of functional study the penile crura were collected from rats for molecular and immunohistochemical studies.


RESULTS
Mean intracavernous pressure of diabetic rats was significantly lower than in control rats and the decrease in intracavernous pressure was significantly recovered by insulin treatment. Gene expressions of pro-apoptotic and anti-apoptotic factors were present in control, diabetic and insulin treated rat crura. However, anti-apoptotic protein expression was lacking in diabetic rat crura and pro-apoptotic protein expression was lost in insulin treated rat crura. The apoptotic index of diabetic rat crura was significantly higher than that of control rat crura and this index was significantly decreased in insulin treated rat crura.


CONCLUSIONS
There was a significant correlation between the decrease and recovery in intracavernous pressure, and protein expression of apoptotic factors in diabetic and insulin treated rat crura. To our knowledge this is the first report demonstrating that the relief of diabetes associated erectile dysfunction by insulin treatment is due to alterations in the protein expression of apoptotic factors in rat crura.
Yamanaka
Masaki
M
Department of Urology, Veterans Affairs Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Shirai
Masato
M
Shiina
Hiroaki
H
Tanaka
Yuichiro
Y
Tsujimura
Akira
A
Matsumiya
Kiyomi
K
Okuyama
Akihiko
A
Dahiya
Rajvir
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D010413:Penis / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction