Effect of chronic administration of PDE5 inhibitor combined with glycemic control on erectile function in rats with overt erectile dysfunction following induction of diabetes
Streptozotocin 유도 당뇨병 백서에서 type 5 phosphodiesterase (PDE5) 억제제 지속투여와 인슐린 치료의 병합요법이 발기능에 미치는 영향
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2015. 2. 김수웅.
- Introduction: Chronic treatment with type 5 phosphodiesterase inhibitors (PDE5I) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED. We evaluated the effect of chronic administration of PDE5I combined with glycemic control on DMED.
Methods: Sprague–Dawley rats (8-weeks-old) were divided into five groups (n=10 each): normal control (C), diabetes (DM), DM treated with insulin (DM-I), DM treated with PDE5I (DM-P), and DM treated with insulin and PDE5I (DM-I+P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM-I group was treated with a daily injection of neutral protamine Hagedorn, and the DM-P group was treated with a daily dosage of 20 mg/kg PDE5I (DA-8159) for 4 weeks. The DM-I+P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed.
Results: Rats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM-I and DM-P groups showed intermediate erectile function between the DM and C groups. Rats in the DM-I+P group showed restored erectile function, comparable to group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of eNOS and Akt displayed a similar pattern with the results from cavernosometry (DM < DM-I = DM-P < DM-I+P = C, p<0.05). The distribution of phosphorylated MYPT was in the reverse order.
Conclusions: Chronic administration of PDE5I or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5I.
* This work is published in the Journal of Sexual Medicine (Choi WS, Kown OS, Cho SY, Paick JS, Kim SW. Effect of chronic administration of PDE5 inhibitor combined with glycemic control on erectile function in streptozotocin-induced diabetic rats. J Sex Med. 2014 Nov 20. doi: 10.1111/jsm.12752. [Epub ahead of print]).