PMID- 25411013 OWN - NLM STAT- MEDLINE DCOM- 20150706 LR - 20220409 IS - 1743-6109 (Electronic) IS - 1743-6095 (Linking) VI - 12 IP - 3 DP - 2015 Mar TI - Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin-induced diabetic rats. PG - 600-10 LID - 10.1111/jsm.12752 [doi] AB - INTRODUCTION: Chronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED. AIMS: We evaluated the effect of chronic administration of PDE5 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 PDE5 (DM-P), and DM treated with insulin and PDE5 (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 PDE5 (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. MAIN OUTCOME MEASURES: Erectile function and histological and biochemical markers in corporal tissue. 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 with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase 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 myosin phosphatase target subunit 1 was in the reverse order. CONCLUSIONS: Chronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5. CI - (c) 2014 International Society for Sexual Medicine. FAU - Choi, Woo Suk AU - Choi WS AD - Department of Urology, Konkuk University Hospital, Seoul, Korea. FAU - Kwon, Oh Seong AU - Kwon OS FAU - Cho, Sung Yong AU - Cho SY FAU - Paick, Jae-Seung AU - Paick JS FAU - Kim, Soo Woong AU - Kim SW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141120 PL - Netherlands TA - J Sex Med JT - The journal of sexual medicine JID - 101230693 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Phosphodiesterase 5 Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 5W494URQ81 (Streptozocin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - L5IB4XLY36 (udenafil) SB - IM MH - Animals MH - Blood Glucose MH - Diabetes Mellitus, Experimental/complications/*drug therapy/physiopathology MH - Drug Therapy, Combination MH - Erectile Dysfunction/*drug therapy/etiology/physiopathology MH - Hypoglycemic Agents/*therapeutic use MH - Insulin/*therapeutic use MH - Male MH - Nitric Oxide Synthase Type III/metabolism MH - Penile Erection/drug effects MH - Phosphodiesterase 5 Inhibitors/*therapeutic use MH - Pyrimidines/*therapeutic use MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Streptozocin MH - Sulfonamides/*therapeutic use OTO - NOTNLM OT - Animal Model of Diabetes OT - Diabetes Mellitus OT - Erectile Dysfunction EDAT- 2014/11/21 06:00 MHDA- 2015/07/07 06:00 CRDT- 2014/11/21 06:00 PHST- 2014/11/21 06:00 [entrez] PHST- 2014/11/21 06:00 [pubmed] PHST- 2015/07/07 06:00 [medline] AID - S1743-6095(15)30947-4 [pii] AID - 10.1111/jsm.12752 [doi] PST - ppublish SO - J Sex Med. 2015 Mar;12(3):600-10. doi: 10.1111/jsm.12752. Epub 2014 Nov 20.