Asian Journal of Andrology

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 21  |  Issue : 1  |  Page : 74--79

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes


Zhi-Hua Wan, Yuan-Jie Zhang, Lin Chen, Yong-Lian Guo, Guo-Hao Li, Ding Wu, Yong Wang 
 Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China

Correspondence Address:
Lin Chen
Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014
China

Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.


How to cite this article:
Wan ZH, Zhang YJ, Chen L, Guo YL, Li GH, Wu D, Wang Y. G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes.Asian J Androl 2019;21:74-79


How to cite this URL:
Wan ZH, Zhang YJ, Chen L, Guo YL, Li GH, Wu D, Wang Y. G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes. Asian J Androl [serial online] 2019 [cited 2019 Sep 16 ];21:74-79
Available from: http://www.ajandrology.com/article.asp?issn=1008-682X;year=2019;volume=21;issue=1;spage=74;epage=79;aulast=Wan;type=0